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Topical Collection "Feature Papers in Molecular Biophysics"

Editors

Guest Editor
Prof. Dr. Ian A. Nicholls Website E-Mail
Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden
Phone: +46707576868
Interests: biomimetic systems; complex mixture modelling and spectroscopic studies of biological; synthetic and hybrid systems
Guest Editor
Dr. Vladimir N. Uversky Website E-Mail
Molecular Medicine, University of South Florida, Tampa, USA
Phone: 18139745816
Interests: intrinsically disordered proteins; protein folding; protein misfolding; partially folded proteins; protein aggregation; protein structure; protein function; protein stability; protein biophysics; protein bioinformatics; conformational diseases; protein–ligand interactions; protein–protein interactions; liquid-liquid phase transitions

Topical Collection Information

Dear Colleagues,

As follows from the title, this Topical Collection “Feature Papers in Molecular Biophysics” aims to collect high quality research articles, short communications, and review articles in all the fields of molecular biophysics. Since the aim of this Topical Collection is to illustrate, through selected works, frontier research in molecular biophysics, we encourage Editorial Board Members of the Molecular Biophysics Section of the International Journal of Molecular Sciences to contribute papers reflecting the latest progress in their research field, or to invite relevant experts and colleagues to do so.

Topics include, but are not limited to:

  • molecular structure and dynamics
  • nucleic acid structure and dynamics
  • protein structure and dynamics
  • membrane structure and dynamics
  • biomimetic material structure and dynamics
  • molecular simulations
  • molecular modeling
  • single molecule biophysics
  • biophysical techniques in the study of biomacromolecular and biomimetic systems
  • biomolecular interactions
  • biomimetic material interactions
  • macromolecular structure determination or prediction
  • characterization of disordered proteins and their interactions
  • computational biophysics
  • bioinformatics
  • biophysical and computational approaches to drug design and development
  • advances in molecular biophysical methodologies as well as imaging techniques and data analysis
  • application of biophysical methods

Prof. Dr. Ian A. Nicholls
Dr. Vladimir N. Uversky
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biophysics
  • molecular imprinting
  • molecular simulations
  • molecular structure
  • molecular dynamics
  • molecular mechanics
  • thermodynamics
  • biomolecular interactions
  • protein structure and folding
  • intrinsically disordered proteins
  • structure prediction
  • nucleic acid–protein interactions
  • protein–membrane interactions
  • protein–DNA interactions
  • posttranslational modifications
  • drug–receptor interactions
  • protein design
  • protein engineering
  • protein–ligand binding
  • transmembrane proteins
  • chaperones
  • enzymology
  • molecular recognition
  • molecular modeling
  • membrane dynamics
  • macromolecular structure and dynamics
  • DNA structure and dynamics
  • RNA structure
  • genome structure
  • structure–function relationships
  • ion channels
  • spectroscopic techniques
  • biomolecular NMR
  • inter-molecular interactions
  • X-ray crystallography
  • macromolecular crystallography
  • crystal thermodynamics
  • microcalorimetry
  • transient kinetic techniques
  • fluorescence imaging
  • single-molecule microscopy
  • statistical mechanics
  • computer simulations
  • computational modeling
  • molecular modeling

Published Papers (9 papers)

2019

Open AccessArticle
Robust Sampling of Defective Pathways in Multiple Myeloma
Int. J. Mol. Sci. 2019, 20(19), 4681; https://doi.org/10.3390/ijms20194681 (registering DOI) - 21 Sep 2019
Abstract
We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher’s ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of [...] Read more.
We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher’s ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of the disease, such as the existing difference between bone marrow stromal cells in MM and healthy controls (HC), the gene expression profiling of CD34+ cells in MM and HC, the difference between hyperdiploid and non-hyperdiploid myelomas, and the prediction of the chromosome 13 deletion, to provide a deeper insight into the molecular mechanisms involved in the disease. Our analysis has shown the importance of different altered pathways related to glycosylation, infectious disease, immune system response, different aspects of metabolism, DNA repair, protein recycling and regulation of the transcription of genes involved in the differentiation of myeloid cells. The main difference in genetic pathways between hyperdiploid and non-hyperdiploid myelomas are related to infectious disease, immune system response and protein recycling. Our work provides new insights on the genetic pathways involved in this complex disease and proposes novel targets for future therapies. Full article
Open AccessArticle
Cooperative Binding of KaiB to the KaiC Hexamer Ensures Accurate Circadian Clock Oscillation in Cyanobacteria
Int. J. Mol. Sci. 2019, 20(18), 4550; https://doi.org/10.3390/ijms20184550 - 13 Sep 2019
Abstract
The central oscillator generating cyanobacterial circadian rhythms comprises KaiA, KaiB, and KaiC proteins. Their interactions cause KaiC phosphorylation and dephosphorylation cycles over approximately 24 h. KaiB interacts with phosphorylated KaiC in competition with SasA, an output protein harboring a KaiB-homologous domain. Structural data [...] Read more.
The central oscillator generating cyanobacterial circadian rhythms comprises KaiA, KaiB, and KaiC proteins. Their interactions cause KaiC phosphorylation and dephosphorylation cycles over approximately 24 h. KaiB interacts with phosphorylated KaiC in competition with SasA, an output protein harboring a KaiB-homologous domain. Structural data have identified KaiB–KaiC interaction sites; however, KaiB mutations distal from the binding surfaces can impair KaiB–KaiC interaction and the circadian rhythm. Reportedly, KaiB and KaiC exclusively form a complex in a 6:6 stoichiometry, indicating that KaiB–KaiC hexamer binding shows strong positive cooperativity. Here, mutational analysis was used to investigate the functional significance of this cooperative interaction. Results demonstrate that electrostatic complementarity between KaiB protomers promotes their cooperative assembly, which is indispensable for accurate rhythm generation. SasA does not exhibit such electrostatic complementarity and noncooperatively binds to KaiC. Thus, the findings explain KaiB distal mutation effects, providing mechanistic insights into clock protein interplay. Full article
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Open AccessArticle
Cooperativity and Steep Voltage Dependence in a Bacterial Channel
Int. J. Mol. Sci. 2019, 20(18), 4501; https://doi.org/10.3390/ijms20184501 - 11 Sep 2019
Abstract
This paper reports on the discovery of a novel three-membrane channel unit exhibiting very steep voltage dependence and strong cooperative behavior. It was reconstituted into planar phospholipid membranes formed by the monolayer method and studied under voltage-clamp conditions. The behavior of the novel [...] Read more.
This paper reports on the discovery of a novel three-membrane channel unit exhibiting very steep voltage dependence and strong cooperative behavior. It was reconstituted into planar phospholipid membranes formed by the monolayer method and studied under voltage-clamp conditions. The behavior of the novel channel-former, isolated from Escherichia coli, is consistent with a linearly organized three-channel unit displaying steep voltage-gating (a minimum of 14 charges in the voltage sensor) that rivals that of channels in mammalian excitable membranes. The channels also display strong cooperativity in that closure of the first channel permits the second to close and closure of the second channel permits closure of the third. All three have virtually the same conductance and selectivity, and yet the first and third close at positive potentials whereas the second closes at negative potentials. Thus, is it likely that the second channel-former is oriented in the membrane in a direction opposite to that of the other two. This novel structure is named “triplin.” The extraordinary behavior of triplin indicates that it must have important and as yet undefined physiological roles. Full article
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Open AccessArticle
TRPM6 N-Terminal CaM- and S100A1-Binding Domains
Int. J. Mol. Sci. 2019, 20(18), 4430; https://doi.org/10.3390/ijms20184430 - 09 Sep 2019
Abstract
Transient receptor potential (TRPs) channels are crucial downstream targets of calcium signalling cascades. They can be modulated either by calcium itself and/or by calcium-binding proteins (CBPs). Intracellular messengers usually interact with binding domains present at the most variable TRP regions—N- and C-cytoplasmic termini. [...] Read more.
Transient receptor potential (TRPs) channels are crucial downstream targets of calcium signalling cascades. They can be modulated either by calcium itself and/or by calcium-binding proteins (CBPs). Intracellular messengers usually interact with binding domains present at the most variable TRP regions—N- and C-cytoplasmic termini. Calmodulin (CaM) is a calcium-dependent cytosolic protein serving as a modulator of most transmembrane receptors. Although CaM-binding domains are widespread within intracellular parts of TRPs, no such binding domain has been characterised at the TRP melastatin member—the transient receptor potential melastatin 6 (TRPM6) channel. Another CBP, the S100 calcium-binding protein A1 (S100A1), is also known for its modulatory activities towards receptors. S100A1 commonly shares a CaM-binding domain. Here, we present the first identified CaM and S100A1 binding sites at the N-terminal of TRPM6. We have confirmed the L520-R535 N-terminal TRPM6 domain as a shared binding site for CaM and S100A1 using biophysical and molecular modelling methods. A specific domain of basic amino acid residues (R526/R531/K532/R535) present at this TRPM6 domain has been identified as crucial to maintain non-covalent interactions with the ligands. Our data unambiguously confirm that CaM and S100A1 share the same binding domain at the TRPM6 N-terminus although the ligand-binding mechanism is different. Full article
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Open AccessArticle
Identifying Methylation Pattern and Genes Associated with Breast Cancer Subtypes
Int. J. Mol. Sci. 2019, 20(17), 4269; https://doi.org/10.3390/ijms20174269 - 31 Aug 2019
Abstract
Breast cancer is regarded worldwide as a severe human disease. Various genetic variations, including hereditary and somatic mutations, contribute to the initiation and progression of this disease. The diagnostic parameters of breast cancer are not limited to the conventional protein content and can [...] Read more.
Breast cancer is regarded worldwide as a severe human disease. Various genetic variations, including hereditary and somatic mutations, contribute to the initiation and progression of this disease. The diagnostic parameters of breast cancer are not limited to the conventional protein content and can include newly discovered genetic variants and even genetic modification patterns such as methylation and microRNA. In addition, breast cancer detection extends to detailed breast cancer stratifications to provide subtype-specific indications for further personalized treatment. One genome-wide expression–methylation quantitative trait loci analysis confirmed that different breast cancer subtypes have various methylation patterns. However, recognizing clinically applied (methylation) biomarkers is difficult due to the large number of differentially methylated genes. In this study, we attempted to re-screen a small group of functional biomarkers for the identification and distinction of different breast cancer subtypes with advanced machine learning methods. The findings may contribute to biomarker identification for different breast cancer subtypes and provide a new perspective for differential pathogenesis in breast cancer subtypes. Full article
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Open AccessReview
Structure Determination by Single-Particle Cryo-Electron Microscopy: Only the Sky (and Intrinsic Disorder) is the Limit
Int. J. Mol. Sci. 2019, 20(17), 4186; https://doi.org/10.3390/ijms20174186 - 27 Aug 2019
Abstract
Traditionally, X-ray crystallography and NMR spectroscopy represent major workhorses of structural biologists, with the lion share of protein structures reported in protein data bank (PDB) being generated by these powerful techniques. Despite their wide utilization in protein structure determination, these two techniques have [...] Read more.
Traditionally, X-ray crystallography and NMR spectroscopy represent major workhorses of structural biologists, with the lion share of protein structures reported in protein data bank (PDB) being generated by these powerful techniques. Despite their wide utilization in protein structure determination, these two techniques have logical limitations, with X-ray crystallography being unsuitable for the analysis of highly dynamic structures and with NMR spectroscopy being restricted to the analysis of relatively small proteins. In recent years, we have witnessed an explosive development of the techniques based on Cryo-electron microscopy (Cryo-EM) for structural characterization of biological molecules. In fact, single-particle Cryo-EM is a special niche as it is a technique of choice for the structural analysis of large, structurally heterogeneous, and dynamic complexes. Here, sub-nanometer atomic resolution can be achieved (i.e., resolution below 10 Å) via single-particle imaging of non-crystalline specimens, with accurate 3D reconstruction being generated based on the computational averaging of multiple 2D projection images of the same particle that was frozen rapidly in solution. We provide here a brief overview of single-particle Cryo-EM and show how Cryo-EM has revolutionized structural investigations of membrane proteins. We also show that the presence of intrinsically disordered or flexible regions in a target protein represents one of the major limitations of this promising technique. Full article
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Open AccessArticle
A New Approach for Spontaneous Silver Ions Immobilization onto Casein
Int. J. Mol. Sci. 2019, 20(16), 3864; https://doi.org/10.3390/ijms20163864 - 08 Aug 2019
Abstract
The work presents the kinetic and isotherm studies of silver binding on casein, which was carried out using batch sorption technique. Moreover, the influence of light irradiation on the process was shown. In order to investigate the mechanism of metal ions sorption by [...] Read more.
The work presents the kinetic and isotherm studies of silver binding on casein, which was carried out using batch sorption technique. Moreover, the influence of light irradiation on the process was shown. In order to investigate the mechanism of metal ions sorption by casein the zero, pseudo-first order kinetics and Weber-Morris intra-particle diffusion as well as Langmuir and Freundlich isotherm models were used. Furthermore, to specify more precisely, the possible binding mechanism, the spectroscopic (FT-IR—Fourier Transform Infrared Spectroscopy, Raman), spectrometric (MALDI-TOF MS—Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometry), microscopic (SEM—Scanning Electron Microscope, TEM/EDX—Transmission Electron Microscopy/Energy Dispersive X-ray detector) and thermal (TGA—Thermogravimetric Analysis, DTG—Derivative Thermogravimetry) analysis were performed. Kinetic study indicates that silver binding onto casein is a heterogeneous process with two main stages: initial rapid stage related to surface adsorption onto casein with immediate creation of silver nanoparticles and slower second stage of intraglobular diffusion with silver binding in chelated form (metalloproteins) or ion-exchange form. Spectroscopic techniques confirmed the binding process and MALDI-TOF MS analysis show the dominant contribution of the α-casein in the process. Moreover, the treatment of silver-casein complex by artificial physiological fluids was performed. Full article
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Open AccessCommunication
Non-Ionic Deep Eutectic Liquids: Acetamide–Urea Derived Room Temperature Solvents
Int. J. Mol. Sci. 2019, 20(12), 2857; https://doi.org/10.3390/ijms20122857 - 12 Jun 2019
Cited by 1
Abstract
A family of non-ionic deep eutectic liquids has been developed based upon mixtures of solid N-alkyl derivatives of urea and acetamide that in some cases have melting points below room temperature. The eutectic behaviour and physical characteristics of a series of eleven [...] Read more.
A family of non-ionic deep eutectic liquids has been developed based upon mixtures of solid N-alkyl derivatives of urea and acetamide that in some cases have melting points below room temperature. The eutectic behaviour and physical characteristics of a series of eleven eutectic mixtures are presented, along with a molecular dynamics study-supported hypothesis for the origin of the non-ideal mixing of these substances. Their use as solvents in applications ranging from natural product extraction to organic and polymer synthesis are demonstrated. Full article
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Open AccessArticle
CUBAN, a Case Study of Selective Binding: Structural Details of the Discrimination between Ubiquitin and NEDD8
Int. J. Mol. Sci. 2019, 20(5), 1185; https://doi.org/10.3390/ijms20051185 - 08 Mar 2019
Cited by 1
Abstract
The newly identified CUBAN (Cullin binding domain associating with NEDD8) domain recognizes both ubiquitin and the ubiquitin-like NEDD8. Despite the high similarity between the two molecules, CUBAN shows a clear preference for NEDD8, free and conjugated to cullins. We previously characterized the domain [...] Read more.
The newly identified CUBAN (Cullin binding domain associating with NEDD8) domain recognizes both ubiquitin and the ubiquitin-like NEDD8. Despite the high similarity between the two molecules, CUBAN shows a clear preference for NEDD8, free and conjugated to cullins. We previously characterized the domain structure, both alone and in complex with NEDD8. The results here reported are addressed to investigate the determinants that drive the selective binding of CUBAN towards NEDD8 and ubiquitin. The 15N HSQC NMR perturbation pattern of the labeled CUBAN domain, when combined with either NEDD8 or ubiquitin, shows a clear involvement of hydrophobic residues that characterize the early stages of these interactions. After a slow conformational selection step, hydrophobic and then neutral and polar interactions take place, which drive the correct orientation of the CUBAN domain, leading to differences in the recognition scheme of NEDD8 and ubiquitin. As a result, a cascade of induced fit steps seems to determine the structural preference shown for NEDD8 and therefore the basis of the selectivity of the CUBAN domain. Finally, molecular dynamics analysis was performed to determine by fluctuations the internal flexibility of the CUBAN/NEDD8 complex. We consider that our results, based on a structural investigation mainly focused on the early stages of the recognition, provide a fruitful opportunity to report the different behavior of the same protein with two highly similar binding partners. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Order, Disorder, BAF Complex, and Chromatin Remodeling
Authors: Nashwa El Hadidy and Vladimir N. Uversky

Title: In situ proteolysis condition-induced crystallization of the XcpVWX complex in different crystal lattice
Authors: Jerry Y. Zhang and Zongchao Jia
Affiliation: Department of Biomedical and Molecular Sciences, Queen's University

Title: Structural prerequisites for antimicrobial peptides to induce keratinocyte cell migration
Authors: G. Weindl, et al.

Title: Biophyiscal investigations into the interaction of synthetic anti-LPS peptides with the bacterial phospholipid membrane
Authors: P. Garidel, et al.

Title: Antiinflammatory mode of action of Pep19-2.5
Authors: Klaus Brandenburg, et al.

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