ArticleProceedings of the National Academy of Sciences of the United States of America2001
Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation from HIV-1 Protease.Biochemistry · 2025Article
- PFAS-Biomolecule Interactions: Case Study Using Asclepios Nodes and Automated Workflows in KNIME for Drug Discovery and Toxicology.Methods in molecular biology (Clifton, N.J.) · 2025Article
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- Binding Mechanism of Inhibitors to BRD4 and BRD9 Decoded by Multiple Independent Molecular Dynamics Simulations and Deep Learning.Molecules (Basel, Switzerland) · 2024Article
- Roles of Accelerated Molecular Dynamics Simulations in Predictions of Binding Kinetic Parameters.Mini reviews in medicinal chemistry · 2024Review
- Binding selectivity-dependent molecular mechanism of inhibitors towards CDK2 and CDK6 investigated by multiple short molecular dynamics and free energy landscapes.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Identification Mechanism of BACE1 on Inhibitors Probed by Using Multiple Separate Molecular Dynamics Simulations and Comparative Calculations of Binding Free Energies.Molecules (Basel, Switzerland) · 2023Article
- Searching for potential inhibitors of SARS-COV-2 main protease using supervised learning and perturbation calculations.Chemical physics · 2023Article
- Binding selectivity analysis of AURKs inhibitors through molecular dynamics simulation studies.PloS one · 2023Article
- Identifying Possible AChE Inhibitors from Drug-like Molecules via Machine Learning and Experimental Studies.ACS omega · 2022Article
- Theoretical exploration of the binding selectivity of inhibitors to BRD7 and BRD9 with multiple short molecular dynamics simulations.RSC advances · 2022Article
- Losartan Interactions with 2-Hydroxypropyl-β-CD.Molecules (Basel, Switzerland) · 2022Article
- The evolution of the HIV-1 protease folding stability.Virus evolution · 2022Article
- Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule.Computational and structural biotechnology journal · 2022Article
- Structural determinants for subnanomolar inhibition of the secreted aspartic protease Sapp1p fromJournal of enzyme inhibition and medicinal chemistry · 2021Article
- Molecular dynamics simulations data of six compounds F3J-BRD4/CBP, EX1-BRD4/CBP, and E2T-BRD4/CBP.Data in brief · 2021Article
- Article
- Accurate Prediction of Inhibitor Binding to HIV-1 Protease Using CANDOCK.Frontiers in chemistry · 2021Article
- Mutation-mediated influences on binding of anaplastic lymphoma kinase to crizotinib decoded by multiple replica Gaussian accelerated molecular dynamics.Journal of computer-aided molecular design · 2020Article
- Article
16 more citing papers are in PubMed but not listed here.
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2 authors.
Funding
Abstract
Drug resistance has sharply limited the effectiveness of HIV-1 protease inhibitors in AIDS therapy. It is critically important to understand the basis of this resistance for designing new drugs. We have evaluated the free energy contribution of each residue in the HIV protease in binding to one of its substrates and to the five FDA-approved protease drugs. Analysis of these free energy profiles and the variability at each sequence position suggests: (i) single drug resistance mutations are likely to occur at not well conserved residues if they interact more favorably with drugs than with the substrate; and (ii) resistance-evading drugs should have a free energy profile similar to the substrate and interact most favorably with well conserved residues. We also propose an empirical parameter, called the free energy/variability value, which combines free energy calculation and sequence analysis to suggest possible drug resistance mutations on the protease. The free energy/variability value is defined as the product of one residue's contribution to the binding free energy and the variability of that residue. This parameter can assist in designing resistance-evading drugs for any target.
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