Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Advanced Research in Molecular Modeling of Protein Structure and Functions
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Advanced Research in Molecular Modeling of Protein Structure and Functions

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3745

Special Issue Editor

Dr. Maria Khrenova

E-Mail Website
Guest Editor
1. Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia
2. Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences, Moscow, Russia
Interests: molecular modeling; computational and quantum chemistry; enzymatic reactions; photochemistry; QM/MM
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent developments in computer technologies and methods have made molecular modeling a powerful tool for studying processes in huge systems including biomolecular ones. GPU-accelerated molecular dynamics can operate with simulation times of microseconds that allows rare processes to be tracked. Quantum chemical calculations on both CPU and GPU can now deal with the systems of hundreds of atoms and 1000–2000 basis functions. This gives the opportunity to deepen the understanding of the reaction mechanisms in the active sites of enzymes and photoreceptor proteins as well as large conformational rearrangements of protein structures and the formation of protein complexes with low molecular weight inhibitors or macromolecular compounds. This Special Issue covers both topics related to the development of molecular modeling methods and their applications to biomolecular systems. We mostly focus on molecular dynamics and QM/MM, but related studies are also highly encouraged.

Dr. Maria Khrenova
Guest Editor

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 submissions that pass pre-check are 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.

Keywords

  • molecular modeling
  • QM/MM
  • molecular dynamics
  • DFT
  • enzymatic reactions
  • photoreceptor proteins
  • fluorescent proteins
  • substrate specificity
  • inhibition

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 6659 KiB  
Article
Studying Biomolecular Protein Complexes via Origami and 3D-Printed Models
by Hay Azulay, Inbar Benyunes, Gershon Elber and Nir Qvit
Int. J. Mol. Sci. 2024, 25(15), 8271; https://doi.org/10.3390/ijms25158271 - 29 Jul 2024
Viewed by 597
Abstract
Living organisms are constructed from proteins that assemble into biomolecular complexes, each with a unique shape and function. Our knowledge about the structure–activity relationship of these complexes is still limited, mainly because of their small size, complex structure, fast processes, and changing environment. [...] Read more.
Living organisms are constructed from proteins that assemble into biomolecular complexes, each with a unique shape and function. Our knowledge about the structure–activity relationship of these complexes is still limited, mainly because of their small size, complex structure, fast processes, and changing environment. Furthermore, the constraints of current microscopic tools and the difficulty in applying molecular dynamic simulations to capture the dynamic response of biomolecular complexes and long-term phenomena call for new supplementary tools and approaches that can help bridge this gap. In this paper, we present an approach to comparing biomolecular and origami hierarchical structures and apply it to comparing bacterial microcompartments (BMCs) with spiral-based origami models. Our first analysis compares proteins that assemble the BMC with an origami model called “flasher”, which is the unit cell of an assembled origami model. Then, the BMC structure is compared with the assembled origami model and based on the similarity, a physical scaled-up origami model, which is analogous to the BMC, is constructed. The origami model is translated into a computer-aided design model and manufactured via 3D-printing technology. Finite element analysis and physical experiments of the origami model and 3D-printed parts reveal trends in the mechanical response of the icosahedron, which is constructed from tiled-chiral elements. The chiral elements rotate as the icosahedron expands and we deduce that it allows the BMC to open gates for transmembrane passage of materials. Full article
(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)
►▼ Show Figures

Graphical abstract

10 pages, 2796 KiB  
Article
Molecular Basis of Influence of A501X Mutations in Penicillin-Binding Protein 2 of Neisseria gonorrhoeae Strain 35/02 on Ceftriaxone Resistance
by Alexandra V. Krivitskaya, Maria S. Kuryshkina, Maria Y. Eremina, Ivan V. Smirnov and Maria G. Khrenova
Int. J. Mol. Sci. 2024, 25(15), 8260; https://doi.org/10.3390/ijms25158260 - 29 Jul 2024
Viewed by 419
Abstract
The increase in the resistance of mutant strains of Neisseria gonorrhoeae to the antibiotic ceftriaxone is pronounced in the decrease in the second-order acylation rate constant, k2/KS, by penicillin-binding protein 2 (PBP2). These changes can be caused by both [...] Read more.
The increase in the resistance of mutant strains of Neisseria gonorrhoeae to the antibiotic ceftriaxone is pronounced in the decrease in the second-order acylation rate constant, k2/KS, by penicillin-binding protein 2 (PBP2). These changes can be caused by both the decrease in the acylation rate constant, k2, and the weakening of the binding affinity, i.e., an increase in the substrate constant, KS. A501X mutations in PBP2 affect second-order acylation rate constants. The PBP2A501V variant exhibits a higher k2/KS value, whereas for PBP2A501R and PBP2A501P variants, these values are lower. We performed molecular dynamic simulations with both classical and QM/MM potentials to model both acylation energy profiles and conformational dynamics of four PBP2 variants to explain the origin of k2/KS changes. The acylation reaction occurs in two elementary steps, specifically, a nucleophilic attack by the oxygen atom of the Ser310 residue and C–N bond cleavage in the β-lactam ring accompanied by the elimination of the leaving group of ceftriaxone. The energy barrier of the first step increases for PBP2 variants with a decrease in the observed k2/KS value. Submicrosecond classic molecular dynamic trajectories with subsequent cluster analysis reveal that the conformation of the β3–β4 loop switches from open to closed and its flexibility decreases for PBP2 variants with a lower k2/KS value. Thus, the experimentally observed decrease in the k2/KS in A501X variants of PBP2 occurs due to both the decrease in the acylation rate constant, k2, and the increase in KS. Full article
(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)
►▼ Show Figures

Graphical abstract

14 pages, 3290 KiB  
Article
Saturation Mutagenesis and Molecular Modeling: The Impact of Methionine 182 Substitutions on the Stability of β-Lactamase TEM-1
by Vitaly G. Grigorenko, Alexandra V. Krivitskaya, Maria G. Khrenova, Maya Yu. Rubtsova, Galina V. Presnova, Irina P. Andreeva, Oxana V. Serova and Alexey M. Egorov
Int. J. Mol. Sci. 2024, 25(14), 7691; https://doi.org/10.3390/ijms25147691 - 13 Jul 2024
Viewed by 588
Abstract
Serine β-lactamase TEM-1 is the first β-lactamase discovered and is still common in Gram-negative pathogens resistant to β-lactam antibiotics. It hydrolyzes penicillins and cephalosporins of early generations. Some of the emerging TEM-1 variants with one or several amino acid substitutions have even broader [...] Read more.
Serine β-lactamase TEM-1 is the first β-lactamase discovered and is still common in Gram-negative pathogens resistant to β-lactam antibiotics. It hydrolyzes penicillins and cephalosporins of early generations. Some of the emerging TEM-1 variants with one or several amino acid substitutions have even broader substrate specificity and resistance to known covalent inhibitors. Key amino acid substitutions affect catalytic properties of the enzyme, and secondary mutations accompany them. The occurrence of the secondary mutation M182T, called a “global suppressor”, has almost doubled over the last decade. Therefore, we performed saturating mutagenesis at position 182 of TEM-1 to determine the influence of this single amino acid substitution on the catalytic properties, thermal stability, and ability for thermoreactivation. Steady-state parameters for penicillin, cephalothin, and ceftazidime are similar for all TEM-1 M182X variants, whereas melting temperature and ability to reactivate after incubation at a higher temperature vary significantly. The effects are multidirectional and depend on the particular amino acid at position 182. The M182E variant of β-lactamase TEM-1 demonstrates the highest residual enzymatic activity, which is 1.5 times higher than for the wild-type enzyme. The 3D structure of the side chain of residue 182 is of particular importance as observed from the comparison of the M182I and M182L variants of TEM-1. Both of these amino acid residues have hydrophobic side chains of similar size, but their residual activity differs by three-fold. Molecular dynamic simulations add a mechanistic explanation for this phenomenon. The important structural element is the V159-R65-E177 triad that exists due to both electrostatic and hydrophobic interactions. Amino acid substitutions that disturb this triad lead to a decrease in the ability of the β-lactamase to be reactivated. Full article
(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)
►▼ Show Figures

Figure 1

18 pages, 3962 KiB  
Article
TriplEP-CPP: Algorithm for Predicting the Properties of Peptide Sequences
by Maria Serebrennikova, Ekaterina Grafskaia, Dmitriy Maltsev, Kseniya Ivanova, Pavel Bashkirov, Fedor Kornilov, Pavel Volynsky, Roman Efremov, Eduard Bocharov and Vassili Lazarev
Int. J. Mol. Sci. 2024, 25(13), 6869; https://doi.org/10.3390/ijms25136869 - 22 Jun 2024
Viewed by 874
Abstract
Advancements in medicine and pharmacology have led to the development of systems that deliver biologically active molecules inside cells, increasing drug concentrations at target sites. This improves effectiveness and duration of action and reduces side effects on healthy tissues. Cell-penetrating peptides (CPPs) show [...] Read more.
Advancements in medicine and pharmacology have led to the development of systems that deliver biologically active molecules inside cells, increasing drug concentrations at target sites. This improves effectiveness and duration of action and reduces side effects on healthy tissues. Cell-penetrating peptides (CPPs) show promise in this area. While traditional medicinal chemistry methods have been used to develop CPPs, machine learning techniques can speed up and reduce costs in the search for new peptides. A predictive algorithm based on machine learning models was created to identify novel CPP sequences using molecular descriptors using a combination of algorithms like k-nearest neighbors, gradient boosting, and random forest. Some potential CPPs were found and tested for cytotoxicity and penetrating ability. A new low-toxicity CPP was discovered from the Rhopilema esculentum venom proteome through this study. Full article
(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

25 pages, 6813 KiB  
Review
The Three-Dimensional Reference Interaction Site Model Approach as a Promising Tool for Studying Hydrated Viruses and Their Complexes with Ligands
by Marina V. Fedotova and Gennady N. Chuev
Int. J. Mol. Sci. 2024, 25(7), 3697; https://doi.org/10.3390/ijms25073697 - 26 Mar 2024
Viewed by 815
Abstract
Viruses are the most numerous biological form living in any ecosystem. Viral diseases affect not only people but also representatives of fauna and flora. The latest pandemic has shown how important it is for the scientific community to respond quickly to the challenge, [...] Read more.
Viruses are the most numerous biological form living in any ecosystem. Viral diseases affect not only people but also representatives of fauna and flora. The latest pandemic has shown how important it is for the scientific community to respond quickly to the challenge, including critically assessing the viral threat and developing appropriate measures to counter this threat. Scientists around the world are making enormous efforts to solve these problems. In silico methods, which allow quite rapid obtention of, in many cases, accurate information in this field, are effective tools for the description of various aspects of virus activity, including virus–host cell interactions, and, thus, can provide a molecular insight into the mechanism of virus functioning. The three-dimensional reference interaction site model (3D-RISM) seems to be one of the most effective and inexpensive methods to compute hydrated viruses, since the method allows us to provide efficient calculations of hydrated viruses, remaining all molecular details of the liquid environment and virus structure. The pandemic challenge has resulted in a fast increase in the number of 3D-RISM calculations devoted to hydrated viruses. To provide readers with a summary of this literature, we present a systematic overview of the 3D-RISM calculations, covering the period since 2010. We discuss various biophysical aspects of the 3D-RISM results and demonstrate capabilities, limitations, achievements, and prospects of the method using examples of viruses such as influenza, hepatitis, and SARS-CoV-2 viruses. Full article
(This article belongs to the Special Issue Advanced Research in Molecular Modeling of Protein Structure and Functions)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop