http://www.mdpi.com/journal/ijms/special_issues/molecular-recognition/ Dear Colleagues, Molecular recognition is the specific interaction of one molecule with another by means of noncovalent bonds and hydrophobic effects. Molecular recognition can lead to the formation of a stable or transient complex between the two molecules or can lead to more complex interactions that result in associated allostery, catalysis, or even assembly of molecular machines. The interacting molecular pair can vary widely in size and complexity, from small molecules or even metal ions, to large proteins, nucleic acids, lipid assemblies, and carbohydrates. Molecular recognition is the most fundamental process underpinning life. Virtually every cellular activity can be viewed as a spatially and temporally ordered series of molecular recognition steps involving two or more molecules at each step. Over the years a variety of models have been proposed to explain molecular recognition from the most fundamental level to the highest level of complexity. These models include, for small molecules, stereochemical fit among others, and for biological molecules, the lock and key, induced fit, conformational selection and coupled binding and folding. Recently very detailed computational models are being explored that probe shape, hydrogen bonding, and charge complementarity. Given the recent advances in high level models and in experimental and computational techniques that identify and probe molecular recognition events, it is time for an update in this rapidly advancing area. Prof. Dr. A. Keith Dunker Guest Editor {snippet name="submission_info"} 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/1422-0067/12/3/1431/ 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/1422-0067/11/4/1930/ 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