ArticleInternational journal of molecular sciences2016
Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 34 citations in OpenAlex.
- Advancements in development of novel class of HIV protease inhibitors.Annals of medicine · 2026Review
- Exploring evolutionary trajectories of drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deciphering Complex Mechanisms of Resistance and Loss of Potency through Coupled Molecular Dynamics and Machine Learning.Journal of chemical theory and computation · 2021Article
- Ligand Binding Mechanism and Its Relationship with Conformational Changes in Adenine Riboswitch.International journal of molecular sciences · 2020Article
- Computational Investigation of Structural Dynamics of SARS-CoV-2 Methyltransferase-Stimulatory Factor Heterodimer nsp16/nsp10 Bound to the Cofactor SAM.Frontiers in molecular biosciences · 2020Article
- Inhibition of HIV-1 Protease byEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations.Nucleic acids research · 2019Article
- Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations.RSC advances · 2018Article
- Molecular Dynamics Exploration of Selectivity of Dual Inhibitors 5M7, 65X, and 65Z toward Fatty Acid Binding Proteins 4 and 5.International journal of molecular sciences · 2018Article
- Dynamics revelation of conformational changes and binding modes of heat shock protein 90 induced by inhibitor associations.RSC advances · 2018Article
- Recent Developments and Applications of the MMPBSA Method.Frontiers in molecular biosciences · 2017Review
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Drug resistance of mutations in HIV-1 protease (PR) is the most severe challenge to the long-term efficacy of HIV-1 PR inhibitor in highly active antiretroviral therapy. To elucidate the molecular mechanism of drug resistance associated with mutations (D30N, I50V, I54M, and V82A) and inhibitor (GRL-0519) complexes, we have performed five molecular dynamics (MD) simulations and calculated the binding free energies using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The ranking of calculated binding free energies is in accordance with the experimental data. The free energy spectra of each residue and inhibitor interaction for all complexes show a similar binding model. Analysis based on the MD trajectories and contribution of each residues show that groups R2 and R3 mainly contribute van der Waals energies, while groups R1 and R4 contribute electrostatic interaction by hydrogen bonds. The drug resistance of D30N can be attributed to the decline in binding affinity of residues 28 and 29. The size of Val50 is smaller than Ile50 causes the residue to move, especially in chain A. The stable hydrophobic core, including the side chain of Ile54 in the wild type (WT) complex, became unstable in I54M because the side chain of Met54 is flexible with two alternative conformations. The binding affinity of Ala82 in V82A decreases relative to Val82 in WT. The present study could provide important guidance for the design of a potent new drug resisting the mutation inhibitors.
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