Cited by 105Computational Drug Discovery MethodsProtein Structure and DynamicsProtein Interaction Studies and Fluorescence Analysis

Rigidity Strengthening: A Mechanism for Protein–Ligand Binding

Nguyen, Duc D., Xiao, Tian, Wang, Menglun, Wei, Guo-Wei·2017·Journal of Chemical Information and Modeling

Abstract

Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug and protein design. Based on large scale data sets, we show that protein rigidity strengthening or flexibility reduction is a mechanism in protein-ligand binding. Our approach based solely on rigidity is able to unveil a surprisingly apparently long-range contribution of apparently four residue layers to protein-ligand binding, which has ramifications for drug and protein design. Additionally, the present work reveals that among various pairwise interactions, the short-range ones within the distance of the van der Waals diameter are most important. It is found that the present approach outperforms all other state-of-the-art scoring functions for protein-ligand binding affinity predictions of two benchmark test sets.

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Crossref · 10.1021/acs.jcim.7b00226

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34 of 34 references verified0 citation errors · 0 not checkable

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  • Characterizing non-additive contributions of functional groups helps machine learning-based scoring functions consistently maintain accuracy in binding affinity predictions across a variety of protein-ligand complexes.

    “Such a characterization can help machine learning-based SFs consistently maintain their accuracy in binding affinity predictions for a variety of protein–ligand complexes [19–23].”

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Authors
Nguyen, D. D., Xiao, T., Wang, M., & Wei, G.-W.
Affiliations
Michigan State University (US)
Corresponding author
Wei, Guo-Wei
Venue
Journal of Chemical Information and Modeling
Published
2017-07-12
Volume
57
Issue
7
Pages
1715-1721
ISSN
  • 1549-9596 (ISSN-L)
  • 1549-960X
OpenAlex
W2610142609
Cited by
105
References
34
Citations by year
2026: 4 · 2025: 12 · 2024: 11 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 11 · 2019: 8 · 2018: 4
FWCI
4.72
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Chemical Information and Modeling (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Division of Mathematical Sciences (1721024)
  • Division of Information and Intelligent Systems (1302285)
  • Center for Mathematical Molecular Biosciences Initiative, Michigan State University
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
Keywords
protein-ligand binding, protein rigidity, binding affinity prediction, pairwise interactions, van der Waals interactions, long-range interactions, drug design, protein design
MeSH terms
Ligands, Protein Binding, Proteins, Computational Biology

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