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Special Issue "Computational Studies of Biomolecules, II"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editors

Assoc. Prof. Tatyana Karabencheva-Christova
E-Mail Website
Guest Editor
Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA
Interests: computational chemical biology; enzyme mechanisms; catalytic activity and inhibition; computer-aided drug design; conformational dynamics of proteins and nucleic acids; biomolecular spectroscopy; bioinorganic enzymology
Special Issues and Collections in MDPI journals
Prof. Dr. Christo Z. Christov
E-Mail Website
Guest Editor

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue "Computational Studies of Biomolecules".

Computational chemistry methods are widely applied to study biomolecular structure, mechanisms, dynamics, and functions. Molecular dynamic (MD) simulations methods, quantum mechanic (QM) methods, combined quantum mechanics/molecular mechanics (QM/MM), molecular docking, and other computational techniques have proven to be very useful for the fundamental understanding of structure–function relationships in biomolecules and are also very useful for applications in drug design, chemical biology, and biotechnology. Importantly, the increased computational power and the development of high-performance computing have led to a growth in synergistic computational–experimental studies in the most relevant areas of biomolecular sciences.

This Special Issue aims to attract high-quality contributions exploring modeling biomolecular structure, dynamics, function, and interactions, with the potential to interpret experimental data and applications in drug design and protein design.

Topics of interest:

  • Development and validation of new computational modeling methods
  • Computational studies of proteins structure–function relationships
  • Computational investigations of nucleic acids structure–function relationships
  • Modeling of protein and nucleic acids dynamics
  • Protein docking
  • Protein–ligand interactions
  • Nucleic acid ligand interactions
  • Protein design
  • Computational enzymology–enzymatic reaction mechanisms
  • Proteins homology modeling

Assoc. Pro Tatyana Karabencheva-Christova
Assoc. Pro Christo Christov
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 special issue 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.

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Published Papers (3 papers)

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Research

Article
A Comparative Study to Decipher the Structural and Dynamics Determinants Underlying the Activity and Thermal Stability of GH-11 Xylanases
Int. J. Mol. Sci. 2021, 22(11), 5961; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115961 - 31 May 2021
Viewed by 622
Abstract
With the growing need for renewable sources of energy, the interest for enzymes capable of biomass degradation has been increasing. In this paper, we consider two different xylanases from the GH-11 family: the particularly active GH-11 xylanase from Neocallimastix patriciarum, NpXyn11A, [...] Read more.
With the growing need for renewable sources of energy, the interest for enzymes capable of biomass degradation has been increasing. In this paper, we consider two different xylanases from the GH-11 family: the particularly active GH-11 xylanase from Neocallimastix patriciarum, NpXyn11A, and the hyper-thermostable mutant of the environmentally isolated GH-11 xylanase, EvXyn11TS. Our aim is to identify the molecular determinants underlying the enhanced capacities of these two enzymes to ultimately graft the abilities of one on the other. Molecular dynamics simulations of the respective free-enzymes and enzyme–xylohexaose complexes were carried out at temperatures of 300, 340, and 500 K. An in-depth analysis of these MD simulations showed how differences in dynamics influence the activity and stability of these two enzymes and allowed us to study and understand in greater depth the molecular and structural basis of these two systems. In light of the results presented in this paper, the thumb region and the larger substrate binding cleft of NpXyn11A seem to play a major role on the activity of this enzyme. Its lower thermal stability may instead be caused by the higher flexibility of certain regions located further from the active site. Regions such as the N-ter, the loops located in the fingers region, the palm loop, and the helix loop seem to be less stable than in the hyper-thermostable EvXyn11TS. By identifying molecular regions that are critical for the stability of these enzymes, this study allowed us to identify promising targets for engineering GH-11 xylanases. Eventually, we identify NpXyn11A as the ideal host for grafting the thermostabilizing traits of EvXyn11TS. Full article
(This article belongs to the Special Issue Computational Studies of Biomolecules, II)
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Article
Molecular Mechanism of Small-Molecule Inhibitors in Blocking the PD-1/PD-L1 Pathway through PD-L1 Dimerization
Int. J. Mol. Sci. 2021, 22(9), 4766; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094766 - 30 Apr 2021
Viewed by 526
Abstract
Programmed cell death-1 (PD-1), which is a molecule involved in the inhibitory signal in the immune system and is important due to blocking of the interactions between PD-1 and programmed cell death ligand-1 (PD-L1), has emerged as a promising immunotherapy for treating cancer. [...] Read more.
Programmed cell death-1 (PD-1), which is a molecule involved in the inhibitory signal in the immune system and is important due to blocking of the interactions between PD-1 and programmed cell death ligand-1 (PD-L1), has emerged as a promising immunotherapy for treating cancer. In this work, molecular dynamics simulations were performed on complex systems consisting of the PD-L1 dimer with (S)-BMS-200, (R)-BMS-200 and (MOD)-BMS-200 (i.e., S, R and MOD systems) to systematically evaluate the inhibitory mechanism of BMS-200-related small-molecule inhibitors in detail. Among them, (MOD)-BMS-200 was modified from the original (S)-BMS-200 by replacing the hydroxyl group with a carbonyl to remove its chirality. Binding free energy analysis indicates that BMS-200-related inhibitors can promote the dimerization of PD-L1. Meanwhile, no significant differences were observed between the S and MOD systems, though the R system exhibited a slightly higher energy. Residue energy decomposition, nonbonded interaction, and contact number analyses show that the inhibitors mainly bind with the C, F and G regions of the PD-L1 dimer, while nonpolar interactions of key residues Ile54, Tyr56, Met115, Ala121 and Tyr123 on both PD-L1 monomers are the dominant binding-related stability factors. Furthermore, compared with (S)-BMS-200, (R)-BMS-200 is more likely to form hydrogen bonds with charged residues. Finally, free energy landscape and protein–protein interaction analyses show that the key residues of the PD-L1 dimer undergo remarkable conformational changes induced by (S)-BMS-200, which boosts its intimate interactions. This systematic investigation provides a comprehensive molecular insight into the ligand recognition process, which will benefit the design of new small-molecule inhibitors targeting PD-L1 for use in anticancer therapy. Full article
(This article belongs to the Special Issue Computational Studies of Biomolecules, II)
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Article
Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins
Int. J. Mol. Sci. 2021, 22(5), 2647; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052647 - 05 Mar 2021
Cited by 1 | Viewed by 683
Abstract
Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a [...] Read more.
Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions. Full article
(This article belongs to the Special Issue Computational Studies of Biomolecules, II)
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