http://www.mdpi.com/section/molecular_recognition http://www.mdpi.com/1422-0067/13/1/710/ Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy. http://www.mdpi.com/1422-0067/13/1/710/ Wed, 11 Jan 2012 00:00:00 CET International Journal of Molecular Sciences 2012-01-11 13 1 Article 710 725 1422-0067 Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis 2012-01-11 doi: 10.3390/ijms13010710 Wuhong Li Changhai Liu Guangguo Tan Xinrong Zhang Zhenyu Zhu Yifeng Chai http://www.mdpi.com/1422-0067/12/11/7335/ A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III)-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III)-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP) and pyrophosphate, as well as dipicolinic acid (DPA) which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively. http://www.mdpi.com/1422-0067/12/11/7335/ Wed, 26 Oct 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-10-26 12 11 Article 7335 7351 1422-0067 A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device 2011-10-26 doi: 10.3390/ijms12117335 Bilge Eker Mahmut Deniz Yilmaz Stefan Schlautmann Johannes G. E. Gardeniers Jurriaan Huskens http://www.mdpi.com/1422-0067/12/10/6544/ ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties. http://www.mdpi.com/1422-0067/12/10/6544/ Thu, 06 Oct 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-10-06 12 10 Review 6544 6565 1422-0067 ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition 2011-10-06 doi: 10.3390/ijms12106544 Paolo Piatti Anette Zeilner Alexandra Lusser http://www.mdpi.com/1422-0067/12/9/6357/ We have demonstrated a polymer mediated “bricks and mortar” method for the self-assembly of quantum dots (QDs). This strategy allows QDs to self-assemble into structured aggregates using complementary three-point hydrogen bonding. The resulting nanocomposites have distinct morphologies and inter-particle distances based on the ratio between QDs and polymer. Time resolved photoluminescence measurements showed that the optical properties of the QDs were retained after self-assembly. http://www.mdpi.com/1422-0067/12/9/6357/ Fri, 23 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-23 12 9 Article 6357 6366 1422-0067 Recognition-Mediated Assembly of Quantum Dot Polymer Conjugates with Controlled Morphology 2011-09-23 doi: 10.3390/ijms12096357 Vikas Nandwana Chandramouleeswaran Subramani Serkan Eymur Yi-Cheun Yeh Gulen Yesilbag Tonga Murat Tonga Youngdo Jeong Boqian Yang Michael D. Barnes Graeme Cooke Vincent M. Rotello http://www.mdpi.com/1422-0067/12/9/6329/ This study focuses on the synthesis and characterization of the inclusion complex of β-Cyclodextrin (β-CD) with dicationic ionic liquid, 3,3'-(1,4-Phenylenebis [methylene]) bis(1-methyl-1H-imidazol-3-ium) di(bromide) (PhenmimBr). The inclusion complex was prepared at room temperature utilizing conventional kneading technique. Proton (1H) NMR and 2D (1H–1H) COSY NMR were the primary characterization tools employed to verify the formation of the inclusion complex. COSY spectra showed strong correlations between protons of imidazolium and protons of β-CD which indicates that the imidazolium ring of PhenmimBr has entered the cavity of β-CD. UV absorption indicated that β-CD reacts with PhenmimBr to form a 2:1 β-CD-PhenmimBr complex with an apparent formation constant of 2.61 × 105 mol−2 L2. Other characterization studies such as UV, FT-IR, XRD, TGA, DSC and SEM studies were also used to further support the formation of the β-CD-PhenmimBr inclusion complex. http://www.mdpi.com/1422-0067/12/9/6329/ Fri, 23 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-23 12 9 Article 6329 6345 1422-0067 Conventional Study on Novel Dicationic Ionic Liquid Inclusion with β-Cyclodextrin 2011-09-23 doi: 10.3390/ijms12096329 Sharifah Mohamad Hemavathy Surikumaran Muggundha Raoov Tilagam Marimuthu Kumuthini Chandrasekaram Puvaneswary Subramaniam http://www.mdpi.com/1422-0067/12/9/6293/ In order to obtain structural features of 3-arylpyrimidin-2,4-diones emerged as promising inhibitors of insect γ-aminobutyric acid (GABA) receptor, a set of ligand-/receptor-based 3D-QSAR models for 60 derivatives are generated using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The statistically optimal CoMSIA model is produced with highest q2 of 0.62, r2ncv of 0.97, and r2pred of 0.95. A minor/bulky electronegative hydrophilic polar substituent at the 1-/6-postion of the uracil ring, and bulky substituents at the 3'-, 4'- and 5'-positions of the benzene ring are beneficial for the enhanced potency of the inhibitors as revealed by the obtained 3D-contour maps. Furthermore, homology modeling, molecular dynamics (MD) simulation and molecular docking are also carried out to gain a better understanding of the probable binding modes of these inhibitors, and the results show that residues Ala-183(C), Thr-187(B), Thr-187(D) and Thr-187(E) in the second transmembrane domains of GABA receptor are responsible for the H-bonding interactions with the inhibitor. The good correlation between docking observations and 3D-QSAR analyses further proves the model reasonability in probing the structural features and the binding mode of 3-arylpyrimidin-2,4-dione derivatives within the housefly GABA receptor. http://www.mdpi.com/1422-0067/12/9/6293/ Fri, 23 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-23 12 9 Article 6293 6311 1422-0067 Probing Structural Features and Binding Mode of 3-Arylpyrimidin-2,4-diones within Housefly γ-Aminobutyric Acid (GABA) Receptor 2011-09-23 doi: 10.3390/ijms12096293 Qinfan Li Lihui Zhang Zhi Ma Xiangya Kong Fangfang Wang Hong Zhang Yonghua Wang http://www.mdpi.com/1422-0067/12/9/5908/ Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented. http://www.mdpi.com/1422-0067/12/9/5908/ Wed, 14 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-14 12 9 Review 5908 5945 1422-0067 Molecularly Imprinted Polymers: Present and Future Prospective 2011-09-14 doi: 10.3390/ijms12095908 Giuseppe Vasapollo Roberta Del Sole Lucia Mergola Maria Rosaria Lazzoi Anna Scardino Sonia Scorrano Giuseppe Mele http://www.mdpi.com/1422-0067/12/9/5736/ In this study, we perform a morphological evaluation of the diverse nanostructures formed by varying concentration and amino acid sequence of a unique class of ultrasmall self-assembling peptides. We modified these peptides by replacing the aliphatic amino acid at the C-aliphatic terminus with different aromatic amino acids. We tracked the effect of introducing aromatic residues on self-assembly and morphology of resulting nanostructures. Whereas aliphatic peptides formed long, helical fibers that entangle into meshes and entrap >99.9% water, the modified peptides contrastingly formed short, straight fibers with a flat morphology. No helical fibers were observed for the modified peptides. For the aliphatic peptides at low concentrations, different supramolecular assemblies such as hollow nanospheres and membrane blebs were found. Since the ultrasmall peptides are made of simple, aliphatic amino acids, considered to have existed in the primordial soup, study of these supramolecular assemblies could be relevant to understanding chemical evolution leading to the origin of life on Earth. In particular, we propose a variety of potential applications in bioengineering and nanotechnology for the diverse self-assembled nanostructures. http://www.mdpi.com/1422-0067/12/9/5736/ Wed, 07 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-07 12 9 Article 5736 5746 1422-0067 Ultrasmall Peptides Self-Assemble into Diverse Nanostructures: Morphological Evaluation and Potential Implications 2011-09-07 doi: 10.3390/ijms12095736 Anupama Lakshmanan Charlotte A.E. Hauser http://www.mdpi.com/1422-0067/12/9/5719/ A process for fabricating ordered organic films on large area is presented. The process allows growing sexithiophene ultra-thin films at precise locations on patterned Si/SiOx substrates by driving the orientation of growth. This process combines the parallel local anodic oxidation of Si/SiOx substrates with the selective arrangement of molecular ultra-thin film. The former is used to fabricate silicon oxide arrays of parallel lines of 400 nm in width over an area of 1 cm2. Selective growth arises from the interplay between kinetic growth parameters and preferential interactions with the patterned surface. The result is an ultra-thin film of organic molecules that is conformal to the features of the fabricated motives. http://www.mdpi.com/1422-0067/12/9/5719/ Tue, 06 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-06 12 9 Article 5719 5735 1422-0067 Selective Growth of α-Sexithiophene by Using Silicon Oxides Patterns 2011-09-06 doi: 10.3390/ijms12095719 Cristiano Albonetti Marianna Barbalinardo Silvia Milita Massimiliano Cavallini Fabiola Liscio Jean-François Moulin Fabio Biscarini http://www.mdpi.com/1422-0067/12/9/5641/ Oligonucleotides carrying amino, thiol groups, as well as fluorescein, c-myc peptide sequence and nanogold at internal positions were prepared and used for the assembly of bidimensional DNA arrays. http://www.mdpi.com/1422-0067/12/9/5641/ Fri, 02 Sep 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-09-02 12 9 Article 5641 5651 1422-0067 Functionalization and Self-Assembly of DNA Bidimensional Arrays 2011-09-02 doi: 10.3390/ijms12095641 Alejandra V. Garibotti Sónia Pérez-Rentero Ramon Eritja http://www.mdpi.com/1422-0067/12/8/5406/ Protein self-assembly, through specific, high affinity, and geometrically constraining protein-protein interactions, can control and lead to complex cellular nano-structures. Establishing an understanding of the underlying principles that govern protein self-assembly is not only essential to appreciate the fundamental biological functions of these structures, but could also provide a basis for their enhancement for nano-material applications. The ferritins are a superfamily of well studied proteins that self-assemble into hollow cage-like structures which are ubiquitously found in both prokaryotes and eukaryotes. Structural studies have revealed that many members of the ferritin family can self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve monomers. This review will focus on the structure of members of the ferritin superfamily, the mechanism of ferritin self-assembly and the structure-function relations of these proteins. http://www.mdpi.com/1422-0067/12/8/5406/ Mon, 22 Aug 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-08-22 12 8 Review 5406 5421 1422-0067 Self-Assembly in the Ferritin Nano-Cage Protein Superfamily 2011-08-22 doi: 10.3390/ijms12085406 Yu Zhang Brendan P. Orner http://www.mdpi.com/1422-0067/12/8/5187/ Pentagonal conjugates of tryptophane zipper-forming peptide (CKTWTWTE) with a pentaazacyclopentadecane core (Pentagonal-Gly-Trpzip and Pentagonal-Ala-Trpzip) were synthesized and their self-assembling behaviors were investigated in water. Pentagonal-Gly-Trpzip self-assembled into nanofibers with the width of about 5 nm in neutral water (pH 7) via formation of tryptophane zipper, which irreversibly converted to nanoribbons by heating. In contrast, Pentagonal-Ala-Trpzip formed irregular aggregates in water. http://www.mdpi.com/1422-0067/12/8/5187/ Mon, 15 Aug 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-08-15 12 8 Article 5187 5199 1422-0067 Syntheses and Self-assembling Behaviors of Pentagonal Conjugates of Tryptophane Zipper-Forming Peptide 2011-08-15 doi: 10.3390/ijms12085187 Kazunori Matsuura Kazuya Murasato Nobuo Kimizuka http://www.mdpi.com/1422-0067/12/8/5157/ Bacterial outer membrane proteins, along with a filling lipid molecule can be modified to form stable self-assembled monolayers on gold. The transmembrane domain of Escherichia coli outer membrane protein A has been engineered to create a scaffold protein to which functional motifs can be fused. In earlier work we described the assembly and structure of an antibody-binding array where the Z domain of Staphylococcus aureus protein A was fused to the scaffold protein. Whilst the binding of rabbit polyclonal immunoglobulin G (IgG) to the array is very strong, mouse monoclonal IgG dissociates from the array easily. This is a problem since many immunodiagnostic tests rely upon the use of mouse monoclonal antibodies. Here we describe a strategy to develop an antibody-binding array that will bind mouse monoclonal IgG with lowered dissociation from the array. A novel protein consisting of the scaffold protein fused to two pairs of Z domains separated by a long flexible linker was manufactured. Using surface plasmon resonance the self-assembly of the new protein on gold and the improved binding of mouse monoclonal IgG were demonstrated. http://www.mdpi.com/1422-0067/12/8/5157/ Mon, 15 Aug 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-08-15 12 8 Article 5157 5167 1422-0067 Self-Assembly of Protein Monolayers Engineered for Improved Monoclonal Immunoglobulin G Binding 2011-08-15 doi: 10.3390/ijms12085157 Anton P. Le Brun Deepan S. H. Shah Dale Athey Stephen A. Holt Jeremy H. Lakey http://www.mdpi.com/1422-0067/12/8/4781/ In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects. http://www.mdpi.com/1422-0067/12/8/4781/ Thu, 28 Jul 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-07-28 12 8 Article 4781 4804 1422-0067 Molecular Recognition Effects in Atomistic Models of Imprinted Polymers 2011-07-28 doi: 10.3390/ijms12084781 Eduardo M. A. Dourado Carmelo Herdes Paul R. Van Tassel Lev Sarkisov http://www.mdpi.com/1422-0067/12/8/4758/ Regulation of transcription involves dynamic rearrangements of chromatin structure. The budding yeast Saccharomyces cerevisiae has a variety of highly conserved factors necessary for these reconstructions. Chromatin remodelers, histone modifiers and histone chaperones directly associate to promoters and open reading frames of exposed genes and facilitate activation and repression of transcription. We compare two distinct patterns of induced transcription: Sustained transcribed genes switch to an activated state where they remain as long as the induction signal is present. In contrast, single pulsed transcribed genes show a quick and strong induction pulse resulting in high transcript levels followed by adaptation and repression to basal levels. We discuss intensively studied promoters and coding regions from both groups for their co-factor requirements during transcription. Interplay between chromatin restructuring factors and dynamic transcription is highly variable and locus dependent. http://www.mdpi.com/1422-0067/12/8/4758/ Mon, 25 Jul 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-07-25 12 8 Review 4758 4769 1422-0067 Interplay of Dynamic Transcription and Chromatin Remodeling: Lessons from Yeast 2011-07-25 doi: 10.3390/ijms12084758 Gerhard Niederacher Eva Klopf Christoph Schüller http://www.mdpi.com/1422-0067/12/7/4705/ Reduction in oxygen levels below normal concentrations plays important roles in different normal and pathological conditions, such as development, tumorigenesis, chronic kidney disease and stroke. Organisms exposed to hypoxia trigger changes at both cellular and systemic levels to recover oxygen homeostasis. Most of these processes are mediated by Hypoxia Inducible Factors, HIFs, a family of transcription factors that directly induce the expression of several hundred genes in mammalian cells. Although different aspects of HIF regulation are well known, it is still unclear by which precise mechanism HIFs activate transcription of their target genes. Concomitantly, hypoxia provokes a dramatic decrease of general transcription that seems to rely in part on epigenetic changes through a poorly understood mechanism. In this review we discuss the current knowledge on chromatin changes involved in HIF dependent gene activation, as well as on other epigenetic changes, not necessarily linked to HIF that take place under hypoxic conditions. http://www.mdpi.com/1422-0067/12/7/4705/ Thu, 21 Jul 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-07-21 12 7 Review 4705 4721 1422-0067 Epigenetics: New Questions on the Response to Hypoxia 2011-07-21 doi: 10.3390/ijms12074705 Joel I. Perez-Perri Julieta M. Acevedo Pablo Wappner http://www.mdpi.com/1422-0067/12/7/4637/ In this article we investigate the effect of multivalency in chiral recognition. To this end, we measured the host-guest interaction of a β-cyclodextrin dimer with divalent chiral guests. We report the synthesis of carbohydrate-based water soluble chiral guests functionalized with two borneol, menthol, or isopinocampheol units in either (+) or (–) configuration. We determined the interaction of these divalent guests with a β-cyclodextrin dimer using isothermal titration calorimetry. It was found that—in spite of a highly unfavorable conformation—the cyclodextrin dimer binds to guest dimers with an increased enantioselectivity, which clearly reflects the effect of multivalency. http://www.mdpi.com/1422-0067/12/7/4637/ Mon, 18 Jul 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-07-18 12 7 Article 4637 4646 1422-0067 Enhanced Chiral Recognition by Cyclodextrin Dimers 2011-07-18 doi: 10.3390/ijms12074637 Jens Voskuhl Kira Schaepe Bart Jan Ravoo http://www.mdpi.com/1422-0067/12/7/4327/ Template removal is a critical step in the preparation of most molecularly imprinted polymers (MIPs). The polymer network itself and the affinity of the imprinted cavities for the template make its removal hard. If there are remaining template molecules in the MIPs, less cavities will be available for rebinding, which decreases efficiency. Furthermore, if template bleeding occurs during analytical applications, errors will arise. Despite the relevance to the MIPs performance, template removal has received scarce attention and is currently the least cost-effective step of the MIP development. Attempts to reach complete template removal may involve the use of too drastic conditions in conventional extraction techniques, resulting in the damage or the collapse of the imprinted cavities. Advances in the extraction techniques in the last decade may provide optimized tools. The aim of this review is to analyze the available data on the efficiency of diverse extraction techniques for template removal, paying attention not only to the removal yield but also to MIPs performance. Such an analysis is expected to be useful for opening a way to rational approaches for template removal (minimizing the costs of solvents and time) instead of the current trial-and-error methods. http://www.mdpi.com/1422-0067/12/7/4327/ Tue, 05 Jul 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-07-05 12 7 Review 4327 4347 1422-0067 To Remove or Not to Remove? The Challenge of Extracting the Template to Make the Cavities Available in Molecularly Imprinted Polymers (MIPs) 2011-07-05 doi: 10.3390/ijms12074327 Rosa A. Lorenzo Antonia M. Carro Carmen Alvarez-Lorenzo Angel Concheiro http://www.mdpi.com/1422-0067/12/5/3322/ A molecularly imprinted polymer (MIP), obtained by precipitation polymerisation with 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as cross-linker, and bisphenol-A (BPA) as template, was prepared. The binding site configuration of the BPA-MIP was examined using Scatchard analysis. Moreover, the behaviour of the BPA-MIP for the extraction of several phenolic compounds (bisphenol-A, bisphenol-F, 4-nitrophenol, 3-methyl-4-nitrophenol) and phenoxyacid herbicides such as 2,4-D, 2,4,5-T and 2,4,5-TP has been studied in organic and aqueous media in the presence of other pesticides in common use. It was possible to carry out the selective preconcentration of the target analytes from the organic medium with recoveries of higher than 70%. In an aqueous medium, hydrophobic interactions were found to exert a remarkably non-specific contribution to the overall binding process. Several parameters affecting the extraction efficiency of the BPA-MIP were evaluated to achieve the selective preconcentration of phenols and phenoxyacids from aqueous samples. The possibility of using the BPA-MIP as a selective sorbent to preconcentrate these compounds from other samples such as urine and river water was also explored. http://www.mdpi.com/1422-0067/12/5/3322/ Fri, 20 May 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-05-20 12 5 Article 3322 3339 1422-0067 Behavior of Phenols and Phenoxyacids on a Bisphenol-A Imprinted Polymer. Application for Selective Solid-Phase Extraction from Water and Urine Samples 2011-05-20 doi: 10.3390/ijms12053322 Eliseo Herrero-Hernández Rita Carabias-Martínez Encarnacion Rodríguez-Gonzalo http://www.mdpi.com/1422-0067/12/5/2853/ A successful design of peptidomimetics must come to terms with χ-space control. The incorporation of χ-space constrained amino acids into bioactive peptides renders the χ1 and χ2 torsional angles of pharmacophore amino acids critical for activity and selectivity as with other relevant structural features of the template. This review describes histidine analogues characterized by replacement of native α and/or β-hydrogen atoms with alkyl substituents as well as analogues with α, β-didehydro unsaturation or Cα-Cβ cyclopropane insertion (ACC derivatives). Attention is also dedicated to the relevant field of β-aminoacid chemistry by describing the synthesis of β2- and β3-models (β-hHis). Structural modifications leading to cyclic imino derivatives such as spinacine, aza-histidine and analogues with shortening or elongation of the native side chain (nor-histidine and homo-histidine, respectively) are also described. Examples of the use of the described analogues to replace native histidine in bioactive peptides are also given. http://www.mdpi.com/1422-0067/12/5/2853/ Tue, 03 May 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-05-03 12 5 Review 2853 2890 1422-0067 Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control 2011-05-03 doi: 10.3390/ijms12052853 Azzurra Stefanucci Francesco Pinnen Federica Feliciani Ivana Cacciatore Gino Lucente Adriano Mollica http://www.mdpi.com/1422-0067/12/4/2315/ Arginine plays an important role in cell division and the functioning of the immune system. We describe a novel method by which arginine can be identified using an artificial monolayer based on surface plasmon resonance (SPR). The affinity of arginine binding its recognition molecular was compared to that of lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether monolayer was anchored onto a gold surface and then characterized by Fourier Transform infrared reflection absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The interaction between arginine and its host compound was investigated by SPR. The calix[4]crown ether was found to assemble as a monolayer on the gold surface. Recognition of calix[4]crown monolayer was assessed by the selective binding of arginine. Modification of the SPR chip with the calix[4]crown monolayer provides a reliable and simple experimental platform for investigation of arginine under aqueous conditions. http://www.mdpi.com/1422-0067/12/4/2315/ Mon, 04 Apr 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-04-04 12 4 Article 2315 2324 1422-0067 Molecular Recognition of Arginine by Supramolecular Complexation with Calixarene Crown Ether Based on Surface Plasmon Resonance 2011-04-04 doi: 10.3390/ijms12042315 Hongxia Chen Limin Gu Yongmei Yin Kwangnak Koh Jaebeom Lee http://www.mdpi.com/1422-0067/12/4/2232/ The reaction of [Ni(L)]Cl2·2H2O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo [14,4,01.18,07.12]docosane) with trans-1,2-cyclopentanedicarboxylic acid (H2-cpdc) yields a 1D hydrogen-bonded infinite chain with formula [Ni(L)(H-cpdc-)2] (1). This complex has been characterized by X-ray crystallography, spectroscopy and cyclic voltammetry. The crystal structure of 1 exhibits a distorted octahedral geometry about Ni atom with four nitrogen atoms of the macrocycle and two oxygen atoms of the H-cpdc- ligand at the axial position. Compound 1 crystallizes in the monoclinic system P21/c with a = 8.7429(17), b = 10.488(2), c = 18.929(4) Å, β = 91.82(2), V = 1734.8(6) Å3, Z = 2. Electronic spectrum of 1 reveals a high-spin octahedral environment. Cyclic voltammetry of 1 undergoes two waves of a one-electron transfer corresponding to NiII/NiIII and NiII/NiI processes. http://www.mdpi.com/1422-0067/12/4/2232/ Fri, 01 Apr 2011 00:00:00 CEST International Journal of Molecular Sciences 2011-04-01 12 4 Article 2232 2241 1422-0067 One-Dimensional Hydrogen-Bonded Infinite Chain from Nickel(II) Tetraaza Macrocyclic Complex and 1,2-Cyclopentanedicarboxylate Ligand 2011-04-01 doi: 10.3390/ijms12042232 In-Taek Lim Ki-Young Choi http://www.mdpi.com/1422-0067/12/3/2019/ The cholesteryl-ester transfer protein (CETP) facilitates the transfer of cholesterol esters and triglycerides between lipoproteins in plasma where the critical site for its function is situated in the C-terminal domain. Our group has previously shown that this domain presents conformational changes in a non-lipid environment when the mutation D470N is introduced. Using a series of peptides derived from this C-terminal domain, the present study shows that these changes favor the induction of a secondary β-structure as characterized by spectroscopic analysis and fluorescence techniques. From this type of secondary structure, the formation of peptide aggregates and fibrillar structures with amyloid characteristics induced cytotoxicity in microglial cells in culture. These supramolecular structures promote cell cytotoxicity through the formation of reactive oxygen species (ROS) and change the balance of a series of proteins that control the process of endocytosis, similar to that observed when β-amyloid fibrils are employed. Therefore, a fine balance between the highly dynamic secondary structure of the C-terminal domain of CETP, the net charge, and the physicochemical characteristics of the surrounding microenvironment define the type of secondary structure acquired. Changes in this balance might favor misfolding in this region, which would alter the lipid transfer capacity conducted by CETP, favoring its propensity to substitute its physiological function. http://www.mdpi.com/1422-0067/12/3/2019/ Mon, 21 Mar 2011 00:00:00 CET International Journal of Molecular Sciences 2011-03-21 12 3 Article 2019 2035 1422-0067 Amyloidogenic Properties of a D/N Mutated 12 Amino Acid Fragment of the C-Terminal Domain of the Cholesteryl-Ester Transfer Protein (CETP) 2011-03-21 doi: 10.3390/ijms12032019 Victor García-González Jaime Mas-Oliva http://www.mdpi.com/1422-0067/12/3/1979/ The principles obtained from studies on molecular chaperones have provided explanations for the assisted protein folding in vivo. However, the majority of proteins can fold without the assistance of the known molecular chaperones, and little attention has been paid to the potential chaperoning roles of other macromolecules. During protein biogenesis and folding, newly synthesized polypeptide chains interact with a variety of macromolecules, including ribosomes, RNAs, cytoskeleton, lipid bilayer, proteolytic system, etc. In general, the hydrophobic interactions between molecular chaperones and their substrates have been widely believed to be mainly responsible for the substrate stabilization against aggregation. Emerging evidence now indicates that other features of macromolecules such as their surface charges, probably resulting in electrostatic repulsions, and steric hindrance, could play a key role in the stabilization of their linked proteins against aggregation. Such stabilizing mechanisms are expected to give new insights into our understanding of the chaperoning functions for de novo protein folding. In this review, we will discuss the possible chaperoning roles of these macromolecules in de novo folding, based on their charge and steric features. http://www.mdpi.com/1422-0067/12/3/1979/ Fri, 18 Mar 2011 00:00:00 CET International Journal of Molecular Sciences 2011-03-18 12 3 Review 1979 1990 1422-0067 Chaperoning Roles of Macromolecules Interacting with Proteins in Vivo 2011-03-18 doi: 10.3390/ijms12031979 Seong Il Choi Keo-Heun Lim Baik L. Seong http://www.mdpi.com/1422-0067/12/3/1464/ Self-assembled nanostructures of zwitterionic octaphosphanatoporphyrin 1, of either nanoparticles or nanorods, depending on small changes in the pH, is demonstrated based on the J-aggregates. Porphyrin 1 self-assembled into nanosphere aggregates with a diameter of about 70–80 nm in the pH range 5–7, and nanorod aggregates were observed at pH 8.5. Hydrogen bonding, p-p stacking and hydrophilic interactions play important roles in the formation of this nanostructure morphology. Nanostructures were characterized by UV/Vis absorbance, fluorescence, atomic force microscopy (AFM) and transmission electron microscopy (TEM). This interesting pH dependent self-assembly phenomenon could provide a basis for development of novel biomaterials. http://www.mdpi.com/1422-0067/12/3/1464/ Thu, 24 Feb 2011 00:00:00 CET International Journal of Molecular Sciences 2011-02-24 12 3 Article 1464 1473 1422-0067 pH Dependent Molecular Self-Assembly of Octaphosphonate Porphyrin of Nanoscale Dimensions: Nanosphere and Nanorod Aggregates 2011-02-24 doi: 10.3390/ijms12031464 Sheshanath V. Bhosale Mohan B. Kalyankar Santosh V. Nalage Cecilia H. Lalander Sidhanath V. Bhosale Steven J. Langford Ruth F. Oliver http://www.mdpi.com/1422-0067/12/3/1431/ Proteins are uniquely capable of identifying targets with unparalleled selectivity, but, in addition to the precision of the binding phenomenon, nature has the ability to find its targets exceptionally quickly. Transcription factors for instance can bind to a specific sequence of nucleic acids from a soup of similar, but not identical DNA strands, on a timescale of seconds. This is only possible with the enhanced kinetics provided for by a natively disordered structure, where protein folding and binding are cooperative processes. The secondary structures of many proteins are disordered under physiological conditions. Subsequently, the disordered structures fold into ordered structures only when they bind to their specific targets. Induced folding of the protein has two key biological advantages. First, flexible unstructured domains can result in an intrinsic plasticity that allows them to accommodate targets of various size and shape. And, second, the dynamics of this folding process can result in enhanced binding kinetics. Several groups have hypothesized the acceleration of binding kinetics is due to induced folding where a “fly-casting” effect has been shown to break the diffusion-limited rate of binding. This review describes experimental results in rationally designed peptide systems where the folding is coupled to amphiphilicity and biomolecular activity. http://www.mdpi.com/1422-0067/12/3/1431/ Thu, 24 Feb 2011 00:00:00 CET International Journal of Molecular Sciences 2011-02-24 12 3 Review 1431 1450 1422-0067 Coupled Folding and Specific Binding: Fishing for Amphiphilicity 2011-02-24 doi: 10.3390/ijms12031431 Vikas P. Jain Raymond S. Tu http://www.mdpi.com/1422-0067/12/2/1410/ Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs) which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N) which are involved in binding with two different targets (MDM2 and Taz2), and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex). We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs). http://www.mdpi.com/1422-0067/12/2/1410/ Wed, 23 Feb 2011 00:00:00 CET International Journal of Molecular Sciences 2011-02-23 12 2 Article 1410 1430 1422-0067 Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein 2011-02-23 doi: 10.3390/ijms12021410 Yongqi Huang Zhirong Liu http://www.mdpi.com/1422-0067/12/2/1316/ Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success. http://www.mdpi.com/1422-0067/12/2/1316/ Tue, 22 Feb 2011 00:00:00 CET International Journal of Molecular Sciences 2011-02-22 12 2 Review 1316 1333 1422-0067 Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking 2011-02-22 doi: 10.3390/ijms12021316 Karine Bastard Adrien Saladin Chantal Prévost http://www.mdpi.com/1422-0067/12/1/334/ The mechanisms of chronic infections caused by opportunistic pathogens are of keen interest to both researchers and health professionals globally. Typically, chronic infectious disease can be characterized by an elevation in immune response, a process that can often lead to further destruction. Reactive-Oxygen-Species (ROS) have been strongly implicated in the aforementioned detrimental response by host that results in self-damage. Unlike excessive ROS production resulting in robust cellular death typically induced by acute infection or inflammation, lower levels of ROS produced by host cells are increasingly recognized to play a critical physiological role for regulating a variety of homeostatic cellular functions including growth, apoptosis, immune response, and microbial colonization. Sources of cellular ROS stimulation can include “danger-signal-molecules” such as extracellular ATP (eATP) released by stressed, infected, or dying cells. Particularly, eATP-P2X7 receptor mediated ROS production has been lately found to be a key modulator for controlling chronic infection and inflammation. There is growing evidence that persistent microbes can alter host cell ROS production and modulate eATP-induced ROS for maintaining long-term carriage. Though these processes have yet to be fully understood, exploring potential positive traits of these “injurious” molecules could illuminate how opportunistic pathogens maintain persistence through physiological regulation of ROS signaling. http://www.mdpi.com/1422-0067/12/1/334/ Thu, 13 Jan 2011 00:00:00 CET International Journal of Molecular Sciences 2011-01-13 12 1 Review 334 352 1422-0067 The Role of Reactive-Oxygen-Species in Microbial Persistence and Inflammation 2011-01-13 doi: 10.3390/ijms12010334 Ralee Spooner Özlem Yilmaz http://www.mdpi.com/1422-0067/12/1/226/ Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results. http://www.mdpi.com/1422-0067/12/1/226/ Wed, 05 Jan 2011 00:00:00 CET International Journal of Molecular Sciences 2011-01-05 12 1 Article 226 251 1422-0067 Computational Docking of Antibody-Antigen Complexes, Opportunities and Pitfalls Illustrated by Influenza Hemagglutinin 2011-01-05 doi: 10.3390/ijms12010226 Mattia Pedotti Luca Simonelli Elsa Livoti Luca Varani http://www.mdpi.com/1422-0067/11/12/5292/ Intrinsically disordered proteins (IDPs) are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs. http://www.mdpi.com/1422-0067/11/12/5292/ Tue, 21 Dec 2010 00:00:00 CET International Journal of Molecular Sciences 2010-12-21 11 12 Review 5292 5309 1422-0067 Intrinsically Disordered Proteins in a Physics-Based World 2010-12-21 doi: 10.3390/ijms11125292 Timothy H. Click Debabani Ganguly Jianhan Chen http://www.mdpi.com/1422-0067/11/12/5212/ Deleted in Malignant Brain Tumors-1 protein (DMBT1), salivary agglutinin (DMBT1SAG), and lung glycoprotein-340 (DMBT1GP340) are three names for glycoproteins encoded by the same DMBT1 gene. All these proteins belong to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins: a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. In addition to SRCR domains, all DMBT1s contain two CUB domains and one zona pellucida domain. The SRCR domains play a role in the function of DMBT1s, which is the binding of a broad range of pathogens including cariogenic streptococci, Helicobacter pylori and HIV. Mucosal defense proteins like IgA, surfactant proteins and lactoferrin also bind to DMBT1s through their SRCR domains. The binding motif on the SRCR domains comprises an 11-mer peptide in which a few amino acids are essential for binding (GRVEVLYRGSW). Adjacent to each individual SRCR domain are glycosylation domains, where the attached carbohydrate chains play a role in the binding of influenza A virus and Helicobacter pylori. The composition of the carbohydrate chains is not only donor specific, but also varies between different organs. These data demonstrate a role for DMBT1s as pattern recognition molecules containing various peptide and carbohydrate binding motifs. http://www.mdpi.com/1422-0067/11/12/5212/ Fri, 17 Dec 2010 00:00:00 CET International Journal of Molecular Sciences 2010-12-17 11 12 Review 5212 5233 1422-0067 Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites 2010-12-17 doi: 10.3390/ijms1112521 Antoon J. M. Ligtenberg Niclas G. Karlsson Enno C. I. Veerman http://www.mdpi.com/1422-0067/11/12/5129/ Studies on the regulation of phage Ø29 gene expression revealed a new mechanism to accomplish simultaneous activation and repression of transcription leading to orderly gene expression. Two phage-encoded early proteins, p4 and p6, bind synergistically to DNA, modifying the topology of the sequences encompassing early promoters A2c and A2b and late promoter A3 in a hairpin that allows the switch from early to late transcription. Protein p6 is a nucleoid-like protein that binds DNA in a non-sequence specific manner. Protein p4 is a sequence-specific DNA binding protein with multifaceted sequence-readout properties. The protein recognizes the chemical signature of only one DNA base on the inverted repeat of its target sequence through a direct-readout mechanism. In addition, p4 specific binding depends on the recognition of three A-tracts by indirect-readout mechanisms. The biological importance of those three A-tracts resides in their individual properties rather than in the global curvature that they may induce. http://www.mdpi.com/1422-0067/11/12/5129/ Mon, 13 Dec 2010 00:00:00 CET International Journal of Molecular Sciences 2010-12-13 11 12 Article 5129 5142 1422-0067 Molecular Interactions and Protein-Induced DNA Hairpin in the Transcriptional Control of Bacteriophage Ø29 DNA 2010-12-13 doi: 10.3390/ijms11125129 Ana Camacho Margarita Salas http://www.mdpi.com/1422-0067/11/12/5009/ Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group. http://www.mdpi.com/1422-0067/11/12/5009/ Mon, 06 Dec 2010 00:00:00 CET International Journal of Molecular Sciences 2010-12-06 11 12 Article 5009 5026 1422-0067 Binding Ligand Prediction for Proteins Using Partial Matching of Local Surface Patches 2010-12-06 doi: 10.3390/ijms11125009 Lee Sael Daisuke Kihara http://www.mdpi.com/1422-0067/11/12/4991/ O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability. http://www.mdpi.com/1422-0067/11/12/4991/ Fri, 03 Dec 2010 00:00:00 CET International Journal of Molecular Sciences 2010-12-03 11 12 Article 4991 5008 1422-0067 Computational Prediction of O-linked Glycosylation Sites that Preferentially Map on Intrinsically Disordered Regions of Extracellular Proteins 2010-12-03 doi: 10.3390/ijms11124991 Ikuko Nishikawa Yukiko Nakajima Masahiro Ito Satoshi Fukuchi Keiichi Homma Ken Nishikawa http://www.mdpi.com/1422-0067/11/12/4864/ Fumonisins are mycotoxins produced by Fusarium verticillioides and F. proliferatum, fungi that are ubiquitous in corn (maize). Insect damage and some other environmental conditions result in the accumulation of fumonisins in corn-based products worldwide. Current methods of fumonisin detection rely on the use of immunoaffinity columns and high-performance liquid chromatography (HPLC). The use of aptamers offers a good alternative to the use of antibodies in fumonisin cleanup and detection due to lower costs and improved stability. Aptamers are single-stranded oligonucleotides that are selected using Systematic Evolution of Ligands by EXponential enrichment (SELEX) for their ability to bind to targets with high affinity and specificity. Sequences obtained after 18 rounds of SELEX were screened for their ability to bind to fumonisin B1. Six unique sequences were obtained, each showing improved binding to fumonisin B1 compared to controls. Sequence FB1 39 binds to fumonisin with a dissociation constant of 100 ± 30 nM and shows potential for use in fumonisin biosensors and solid phase extraction columns. http://www.mdpi.com/1422-0067/11/12/4864/ Fri, 26 Nov 2010 00:00:00 CET International Journal of Molecular Sciences 2010-11-26 11 12 Article 4864 4881 1422-0067 Screening and Initial Binding Assessment of Fumonisin B1 Aptamers 2010-11-26 doi: 10.3390/ijms11124864 Maureen McKeague Charlotte R. Bradley Annalisa De Girolamo Angelo Visconti J. David Miller Maria C. DeRosa http://www.mdpi.com/1422-0067/11/10/3725/ Many cell functions in all living organisms rely on protein-based molecular recognition involving disorder-to-order transitions upon binding by molecular recognition features (MoRFs). A well accepted computational tool for identifying likely protein-protein interactions is sequence alignment. In this paper, we propose the combination of sequence alignment and disorder prediction as a tool to improve the confidence of identifying MoRF-based protein-protein interactions. The method of reverse sequence alignment is also rationalized here as a novel approach for finding additional interaction regions, leading to the concept of a retro-MoRF, which has the reversed sequence of an identified MoRF. The set of retro-MoRF binding partners likely overlap the partner-sets of the originally identified MoRFs. The high abundance of MoRF-containing intrinsically disordered proteins in nature suggests the possibility that the number of retro-MoRFs could likewise be very high. This hypothesis provides new grounds for exploring the mysteries of protein-protein interaction networks at the genome level. http://www.mdpi.com/1422-0067/11/10/3725/ Wed, 29 Sep 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-09-29 11 10 Article 3725 3747 1422-0067 Retro-MoRFs: Identifying Protein Binding Sites by Normal and Reverse Alignment and Intrinsic Disorder Prediction 2010-09-29 doi: 10.3390/ijms11103725 Bin Xue A. Keith Dunker Vladimir N. Uversky http://www.mdpi.com/1422-0067/11/10/3623/ Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking. http://www.mdpi.com/1422-0067/11/10/3623/ Tue, 28 Sep 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-09-28 11 10 Article 3623 3648 1422-0067 SwarmDock and the Use of Normal Modes in Protein-Protein Docking 2010-09-28 doi: 10.3390/ijms11103623 Iain H. Moal Paul A. Bates http://www.mdpi.com/1422-0067/11/9/3334/ Many carboxylic molecules, ranging from drugs to flavors and fragrances, contain chiral centers. As a consequence, research has been carried out in order to design and synthesize artificial receptors for carboxylic anions. Many problems have to be solved for binding anions. The results obtained in the binding of carboxylic anions by guanidine, secondary ammonium and metal-center have been selected. The last part of this review focuses on chiral recognition of carboxylic anions by organic and metal-based chiral receptors. http://www.mdpi.com/1422-0067/11/9/3334/ Wed, 15 Sep 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-09-15 11 9 Review 3334 3348 1422-0067 Recognition of Chiral Carboxylic Anions by Artificial Receptors 2010-09-15 doi: 10.3390/ijms11093334 Pape Sylla Dieng Claude Sirlin http://www.mdpi.com/1422-0067/11/9/3177/ The dimerization of the cationic β-hairpin antimicrobial peptide protegrin-1 (PG1) is investigated in three different environments: water, the surface of a lipid bilayer membrane, and the core of the membrane. PG1 is known to kill bacteria by forming oligomeric membrane pores, which permeabilize the cells. PG1 dimers are found in two distinct, parallel and antiparallel, conformations, known as important intermediate structural units of the active pore oligomers. What is not clear is the sequence of events from PG1 monomers in solution to pores inside membranes. The step we focus on in this work is the dimerization of PG1. In particular, we are interested in determining where PG1 dimerization is most favorable. We use extensive molecular dynamics simulations to determine the potential of mean force as a function of distance between two PG1 monomers in the aqueous subphase, the surface of model lipid bilayers and the interior of these bilayers. We investigate the two known distinct modes of dimerization that result in either a parallel or an antiparallel β-sheet orientation. The model bilayer membranes are composed of anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) in a 1:3 ratio (POPG:POPE). We find the parallel PG1 dimer association to be more favorable than the antiparallel one in water and inside the membrane. However, we observe that the antiparallel PG1 β-sheet dimer conformation is somewhat more stable than the parallel dimer association at the surface of the membrane. We explore the role of hydrogen bonds and ionic bridges in peptide dimerization in the three environments. Detailed knowledge of how networks of ionic bridges and hydrogen bonds contribute to peptide stability is essential for the purpose of understanding the mechanism of action for membrane-active peptides as well as for designing peptides which can modulate membrane properties. The findings are suggestive of the dominant pathways leading from individual PG1 molecules in solution to functional pores in bacterial membranes. http://www.mdpi.com/1422-0067/11/9/3177/ Thu, 09 Sep 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-09-09 11 9 Article 3177 3194 1422-0067 Dimerization of Protegrin-1 in Different Environments 2010-09-09 doi: 10.3390/ijms11093177 Victor Vivcharuk Yiannis N. Kaznessis http://www.mdpi.com/1422-0067/11/8/3016/ Molecular docking is a widely-used computational tool for the study of molecular recognition, which aims to predict the binding mode and binding affinity of a complex formed by two or more constituent molecules with known structures. An important type of molecular docking is protein-ligand docking because of its therapeutic applications in modern structure-based drug design. Here, we review the recent advances of protein flexibility, ligand sampling, and scoring functions—the three important aspects in protein-ligand docking. Challenges and possible future directions are discussed in the Conclusion. http://www.mdpi.com/1422-0067/11/8/3016/ Wed, 18 Aug 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-08-18 11 8 Review 3016 3034 1422-0067 Advances and Challenges in Protein-Ligand Docking 2010-08-18 doi: 10.3390/ijms11083016 Sheng-You Huang Xiaoqin Zou http://www.mdpi.com/1422-0067/11/5/2241/ In this paper, we present the self assembly procedure as well as experimental results of a novel method for constructing well defined arrangements of self assembly metallic nano particles into sophisticated nano structures. The self assembly concept is based on focused ion beam (FIB) technology, where metallic nano particles are self assembled due to implantation of positive gallium ions into the insulating material (e.g., silica as in silicon on insulator wafers) that acts as intermediary layer between the substrate and the negatively charge metallic nanoparticles. http://www.mdpi.com/1422-0067/11/5/2241/ Tue, 25 May 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-05-25 11 5 Article 2241 2252 1422-0067 Self Assembly of Nano Metric Metallic Particles for Realization of Photonic and Electronic Nano Transistors 2010-05-25 doi: 10.3390/ijms11052242 Shahmoon Limon Girshevitz Zalevsky http://www.mdpi.com/1422-0067/11/4/1930/ Hubs are proteins with a large number of interactions in a protein-protein interaction network. They are the principal agents in the interaction network and affect its function and stability. Their specific recognition of many different protein partners is of great interest from the structural viewpoint. Over the last few years, the structural properties of hubs have been extensively studied. We review the currently known features that are particular to hubs, possibly affecting their binding ability. Specifically, we look at the levels of intrinsic disorder, surface charge and domain distribution in hubs, as compared to non-hubs, along with differences in their functional domains. http://www.mdpi.com/1422-0067/11/4/1930/ Mon, 26 Apr 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-04-26 11 4 Review 1930 1943 1422-0067 Hub Promiscuity in Protein-Protein Interaction Networks 2010-04-26 doi: 10.3390/ijms11041930 Patil Kinoshita Nakamura http://www.mdpi.com/1422-0067/11/4/1808/ Intrinsic cell death is mediated by interaction between pro-apoptotic and pro-survival proteins of the B-cell lymphoma-2 (Bcl-2) family. Members of this family are either intrinsically disordered or contain intrinsically disordered regions/domains that are critical to their function. Alternate splicing and post-translational modifications can determine the extent of these disordered regions and are critical for regulating Bcl-2 proteins. Conformational plasticity and structural transitions characterize the interactions within the Bcl-2 family, with conserved sequence motifs on both binding partners required for their molecular recognition. http://www.mdpi.com/1422-0067/11/4/1808/ Fri, 16 Apr 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-04-16 11 4 Review 1808 1824 1422-0067 Intrinsically Disordered Proteins in Bcl-2 Regulated Apoptosis 2010-04-16 doi: 10.3390/ijms11041808 Rautureau Day Hinds http://www.mdpi.com/1422-0067/11/4/1311/ Photoinduced surface relief grating (SRG) formation for a single crystal of 4-aminoazobenzene was investigated. It was found that SRG could be inscribed on the (001) surface of the crystal, which might suggest that the photoinduced SRG formation is a general phenomenon observed for single crystals of azobenzene-based molecules as well as for azobenzene-based amorphous systems. In addition, the dependences of the SRG formation upon the orientation of the sample crystal and upon the polarization of the writing beams were found to be different from those observed for previously reported crystalline systems. http://www.mdpi.com/1422-0067/11/4/1311/ Tue, 30 Mar 2010 00:00:00 CEST International Journal of Molecular Sciences 2010-03-30 11 4 Article 1311 1320 1422-0067 Photoinduced Surface Relief Grating Formation for a Single Crystal of 4-Aminoazobenzene 2010-03-30 doi: 10.3390/ijms11041311 Nakano http://www.mdpi.com/1422-0067/11/3/1162/ FePt nanoparticles (NPs) were assembled on aluminum oxide substrates, and their ferromagnetic properties were studied before and after thermal annealing. For the first time, phosph(on)ates were used as an adsorbate to form self-assembled monolayers (SAMs) on alumina to direct the assembly of NPs onto the surface. The Al2O3 substrates were functionalized with aminobutylphosphonic acid (ABP) or phosphonoundecanoic acid (PNDA) SAMs or with poly(ethyleneimine) (PEI) as a reference. FePt NPs assembled on all of these monolayers, but much less on unmodified Al2O3, which shows that ligand exchange at the NPs is the most likely mechanism of attachment. Proper modification of the Al2O3 surface and controlling the immersion time of the modified Al2O3 substrates into the FePt NP solution resulted in FePt NPs assembly with controlled NP density. Alumina substrates were patterned by microcontact printing using aminobutylphosphonic acid as the ink, allowing local NP assembly. Thermal annealing under reducing conditions (96%N2/4%H2) led to a phase change of the FePt NPs from the disordered FCC phase to the ordered FCT phase. This resulted in ferromagnetic behavior at room temperature. Such a process can potentially be applied in the fabrication of spintronic devices. http://www.mdpi.com/1422-0067/11/3/1162/ Fri, 19 Mar 2010 00:00:00 CET International Journal of Molecular Sciences 2010-03-19 11 3 Article 1162 1179 1422-0067 Monolayer-directed Assembly and Magnetic Properties of FePt Nanoparticles on Patterned Aluminum Oxide 2010-03-19 doi: 10.3390/iijms11031162 Yildirim Gang Kinge Reinhoudt Blank Van der Wiel Rijnders Huskens http://www.mdpi.com/1422-0067/11/2/754/ Lipid bilayer fusion is a complex process requiring several intermediate steps. Initially, the two bilayers are brought into close contact following removal of intervening water layers and overcoming electrostatic repulsions between opposing bilayer head groups. In this study we monitor by light scattering the reversible aggregation of phosphatidylcholine single shell vesicles during which adhesion occurs but stops prior to a fusion process. Light scattering measurements of dimyristoyl-sn-glycero-3-phosphocholine (DMPC), dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in water show that lowering the temperature of about 0.14 micron single shell vesicles of DPPC (from 20 °C to 5 °C) and about 2 micron vesicles of DSPC (from 20 °C to 15 °C), but not of 1 micron vesicles of DMPC, results in extensive aggregation within 24 hours that is reversible by an increase in temperature. Aggregation of DSPC vesicles was confirmed by direct visual observation. Orientation of lipid head groups parallel to the plane of the bilayer and consequent reduction of the negative surface charge can account for the ability of DPPC and DSPC vesicles to aggregate. Retention of negatively charged phosphates on the surface and the burial of positively charged cholines within the bilayer offer an explanation for the failure of DMPC vesicles to aggregate. Lowering the temperature of 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS) vesicles from 20 °C to 5 °C failed to increase aggregation within 24 hours at Mg++/DPPS ratios that begin to initiate aggregation and fusion. http://www.mdpi.com/1422-0067/11/2/754/ Sun, 21 Feb 2010 00:00:00 CET International Journal of Molecular Sciences 2010-02-21 11 2 Article 754 761 1422-0067 Lipid Vesicle Aggregation Induced by Cooling 2010-02-21 doi: 10.3390/ijms11020754 Frank B. Howard Ira W. Levin http://www.mdpi.com/1422-0067/11/1/288/ We report self-assembly and phase transition behavior of lower diamondoid molecules and their primary derivatives using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. Two lower diamondoids (adamantane and diamantane), three adamantane derivatives (amantadine, memantine and rimantadine) and two artificial molecules (ADM•Na and DIM•Na) are studied separately in 125-molecule simulation systems. We performed DFT calculations to optimize their molecular geometries and obtained atomic electronic charges for the corresponding MD simulation, by which we predicted self-assembly structures and simulation trajectories for the seven different diamondoids and derivatives. Our radial distribution function and structure factor studies showed clear phase transitions and self-assemblies for the seven diamondoids and derivatives. http://www.mdpi.com/1422-0067/11/1/288/ Thu, 21 Jan 2010 00:00:00 CET International Journal of Molecular Sciences 2010-01-21 11 1 Article 288 303 1422-0067 Self-Assembly of Diamondoid Molecules and Derivatives (MD Simulations and DFT Calculations) 2010-01-21 doi: 10.3390/ijms11010288 Yong Xue G. Ali Mansoori http://www.mdpi.com/1422-0067/10/7/2958/ Heterogeneity is a fact that plagues the characterization and application of many self-assembled biological constructs. The importance of obtaining particle homogeneity in biological assemblies is a critical goal, as bulk analysis tools often require identical species for reliable interpretation of the results—indeed, important tools of analysis such as x-ray diffraction typically require over 90% purity for effectiveness. This issue bears particular importance in the case of lipoproteins. Lipid-binding proteins known as apolipoproteins can self assemble with liposomes to form reconstituted high density lipoproteins (rHDLs) or nanolipoprotein particles (NLPs) when used for biotechnology applications such as the solubilization of membrane proteins. Typically, the apolipoprotein and phospholipids reactants are self assembled and even with careful assembly protocols the product often contains heterogeneous particles. In fact, size polydispersity in rHDLs and NLPs published in the literature are frequently observed, which may confound the accurate use of analytical methods. In this article, we demonstrate a procedure for producing a pure, monodisperse NLP subpopulation from a polydisperse self-assembly using size exclusion chromatography (SEC) coupled with high resolution particle imaging by atomic force microscopy (AFM). In addition, NLPs have been shown to self assemble both in the presence and absence of detergents such as cholate, yet the effects of cholate on NLP polydispersity and separation has not been systematically examined. Therefore, we examined the separation properties of NLPs assembled in both the absence and presence of cholate using SEC and native gel electrophoresis. From this analysis, NLPs prepared with and without cholate showed particles with well defined diameters spanning a similar size range. However, cholate was shown to have a dramatic affect on NLP separation by SEC and native gel electrophoresis. Furthermore, under conditions where different sized NLPs were not sufficiently separated or purified by SEC, AFM was used to deconvolute the elution pattern of different sized NLPs. From this analysis we were able to purify an NLP subpopulation to 90% size homogeneity by taking extremely fine elutions from the SEC. With this purity, we generate high quality NLP crystals that were over 100 μm in size with little precipitate, which could not be obtained utilizing the traditional size exclusion techniques. This purification procedure and the methods for validation are broadly applicable to other lipoprotein particles. http://www.mdpi.com/1422-0067/10/7/2958/ Thu, 02 Jul 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-07-02 10 7 Article 2958 2971 1422-0067 Characterization and Purification of Polydisperse Reconstituted Lipoproteins and Nanolipoprotein Particles 2009-07-02 doi: 10.3390/ijms10072958 Craig D. Blanchette Brent W. Segelke Nicholas Fischer Michele H. Corzett Edward A. Kuhn Jenny A. Cappuccio William Henry Benner Matthew A. Coleman Brett A. Chromy Graham Bench Paul D. Hoeprich Todd A. Sulchek http://www.mdpi.com/1422-0067/10/5/2169/ We demonstrate that the temperature-dependent phase behaviors of parallel and perpendicular cylinder-forming block copolymers are governed by domain-domain segregation forces inherently present in block copolymer material itself. With increasing temperature, a parallel cylinder-forming block copolymer experienced a parallel cylinder straightening process before the order-disorder transition (ODT) and did not show long-range composition fluctuations near the ODT temperature due to the weak segregation forces between the block domains. A perpendicular cylinder-forming block copolymer with a strong segregation force between the block domains displayed cylinder orientation transition from perpendicular to parallel below the ODT temperature. On the other hand, a perpendicular cylinder-forming block copolymer material with an exceptionally strong segregation force between the block domains maintained its initial perpendicular cylinder orientation up to near the ODT temperature. In both cases of perpendicular cylinder-forming block copolymers, submicrometer-scale long-range composition fluctuations were observed well above the ODT temperature due to their intrinsically strong segregation forces between the block domains. http://www.mdpi.com/1422-0067/10/5/2169/ Fri, 15 May 2009 00:00:00 CEST International Journal of Molecular Sciences 2009-05-15 10 5 Article 2169 2189 1422-0067 Temperature-Dependent Phase Behaviors in Cylinder-Forming Block Copolymers 2009-05-15 doi: 10.3390/ijms10052169 Dae Up Ahn Erol Sancaktar