ijms-logo

Journal Browser

Journal Browser

Molecular Dynamics Simulations in Enzyme Structure–Function Relationships and Substrate Specificity

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Informatics".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1257

Editor


E-Mail Website
Guest Editor
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130012, China
Interests: the relationship between enzyme structure and function; computer-aided drug design; computational structural biology; machine learning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Enzymes play a central role in a wide range of biological processes and industrial applications, and understanding their structure–function relationships remains a fundamental challenge in biochemistry and molecular biology. In recent years, molecular dynamics (MD) simulations have emerged as a powerful approach to explore enzyme conformational dynamics, substrate recognition, and catalytic mechanisms at atomic resolution.

We are pleased to invite you to contribute to this Special Issue entitled “Molecular Dynamics Simulations in Enzyme Structure–Function Relationships and Substrate Specificity”.

This Special Issue aims to highlight recent advances in the application of molecular simulations and computational approaches to investigate enzyme mechanisms, structure–function relationships, and substrate specificity. Emphasis will be placed on integrating MD simulations with experimental data and emerging computational techniques to deepen our understanding of enzyme function and guide rational enzyme engineering.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Molecular dynamics simulations of enzyme conformational dynamics;
  • Mechanistic insights into enzyme catalysis;
  • Substrate recognition and binding specificity;
  • Structure–function relationship analysis of enzymes;
  • Computational enzyme design and engineering;
  • Enhanced sampling methods (e.g., GaMD, metadynamics);
  • Free energy calculations (MM/PBSA, FEP, etc.);
  • Integration of computational and experimental enzymology;
  • AI-assisted enzyme modeling and prediction;
  • Applications in biotechnology, drug discovery, and food science.

I/We look forward to receiving your contributions. 

Prof. Dr. Weiwei Han
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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 dynamics
  • enzyme mechanism
  • structure–function relationship
  • substrate specificity
  • enzyme engineering
  • free energy calculation
  • computational enzymology
  • protein dynamics
  • molecular modeling

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.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

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

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

18 pages, 45672 KB  
Article
Temperature-Dependent Thumb Domain Dynamics of Xylanase TsaGH11: Insights from Molecular Dynamics Simulations
by Ki Hyun Nam
Int. J. Mol. Sci. 2026, 27(15), 6869; https://doi.org/10.3390/ijms27156869 - 31 Jul 2026
Viewed by 420
Abstract
Xylanases catalyze the hydrolysis of β-1,4-xylosidic linkages in xylan, a major component of plant cell walls, and are widely used in the food, feed, pulp and paper, and biofuel industries. GH11 xylanase from the hemicellulose-degrading bacterium Thermoanaerobacterium saccharolyticum (TsaGH11) exhibits high catalytic activity, [...] Read more.
Xylanases catalyze the hydrolysis of β-1,4-xylosidic linkages in xylan, a major component of plant cell walls, and are widely used in the food, feed, pulp and paper, and biofuel industries. GH11 xylanase from the hemicellulose-degrading bacterium Thermoanaerobacterium saccharolyticum (TsaGH11) exhibits high catalytic activity, making it an attractive enzyme for industrial applications. The flexibility of the thumb domain of TsaGH11 has been investigated under cryogenic and room temperature conditions; however, the substrate recognition mechanism of TsaGH11 at the optimal temperature is unknown. To better understand the molecular mechanism of substrate recognition, the high-resolution crystal structure of TsaGH11 was determined at 1.4 Å resolution. All-atom molecular dynamics simulations at 300, 320, 340, and 360 K revealed that increasing the temperature induced fluctuations in the substrate-recognizing thumb domain. At an optimal temperature of 340 K, the substrate-binding cleft of TsaGH11 predominantly adopted a closed conformation. However, the thumb domain exhibited larger fluctuations at 340 K than at other temperatures, sampling both open and closed conformations, suggesting that substrate recognition in TsaGH11 proceeds through a conformational selection-like mechanism. At 360 K, TsaGH11 unfolded partially at a site opposite the substrate-binding cleft, providing potential targets for protein engineering to improve its thermostability for industrial applications. These findings provide a better understanding of the molecular mechanism of TsaGH11 and offer valuable guidance for the rational engineering of GH11 xylanases for industrial applications. Full article
Show Figures

Figure 1

18 pages, 6042 KB  
Article
Temperature-Dependent Conformational Dynamics of Substrate Entrance Loops in β-Glucosidase: Insights from Molecular Dynamics Simulations
by Ki Hyun Nam
Int. J. Mol. Sci. 2026, 27(10), 4279; https://doi.org/10.3390/ijms27104279 - 11 May 2026
Cited by 2 | Viewed by 514
Abstract
β-Glucosidase (BGL) is widely used in biofuel production, industrial value-added chemicals, and food industry applications. The substrate entrance loops of BGL play a role in substrate specificity and accessibility. To better understand the substrate entrance loops of BGL, a high-resolution crystal structure of [...] Read more.
β-Glucosidase (BGL) is widely used in biofuel production, industrial value-added chemicals, and food industry applications. The substrate entrance loops of BGL play a role in substrate specificity and accessibility. To better understand the substrate entrance loops of BGL, a high-resolution crystal structure of BGL from Thermoanaerobacterium saccharolyticum (TsaBGL) was determined at 1.65 Å, and all-atom molecular dynamics (MD) simulations were performed. The crystal structure of TsaBGL exhibited both folded and straight conformations of the flexible L3 loop, along with rigid conformations of L1, L2, and L4 loops. MD simulations revealed that the folded L3 loop transitioned to a straight conformation, indicating the preference for the straight conformation. At the optimal temperature for enzyme activity, the flexibility of the L3 loop of TsaBGL decreased, whereas that of the L1 loop increased. Moreover, the positions of L1 and L2 loops shifted in a direction opposite to the substrate entrance, resulting in an expanded substrate-binding entrance and increased substrate accessibility to the active site. MD simulations of three homologous BGLs showed that, despite sequence variability, a conserved dynamic trend exists in which the L1 loop exhibits higher flexibility, whereas the L3–L4 loops maintain structural rigidity under optimal conditions. These results provide both an understanding of the loop dynamics involved in substrate accessibility in BGLs and insights into enzyme engineering to improve catalytic performance. Full article
Show Figures

Figure 1

Back to TopTop