ArticleViruses2022
Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation.
Article in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
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- Computational Insights into Flavonoids for ADAMTS-5 Exosite Inhibition in Knee Osteoarthritis: Docking, MD Simulations, and Machine Learning-Guided Structure Prediction.Molecules (Basel, Switzerland) · 2026Article
- Benchmarking Machine Learning Models for HIV-1 Protease Inhibitor Resistance Prediction: Impact of Data Set Construction and Feature Representation.Journal of chemical information and modeling · 2025Article
- A Novel Cystatin Gene from Sea Cucumber (Foods (Basel, Switzerland) · 2025Article
- HIV-1 protease inhibitors and mechanisms of HIV-1's resistance.Global health & medicine · 2024Review
- New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs.Viruses · 2024Review
- Development and emerging trends of drug resistance mutations in HIV: a bibliometric analysis based on CiteSpace.Frontiers in microbiology · 2024Article
- In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1).Current issues in molecular biology · 2023Article
- Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives.Scientific reports · 2023Article
- Anti-proliferative, apoptosis inducing, and antioxidant potential of Callistemon lanceolatus bark extracts: an in vitro and in silico study.Medical oncology (Northwood, London, England) · 2023Article
- Current drugs for HIV-1: from challenges to potential in HIV/AIDS.Frontiers in pharmacology · 2023Review
- Rutin Potentially Binds the Gamma Secretase Catalytic Site, Down Regulates the Notch Signaling Pathway and Reduces Sphere Formation in Colonospheres.Metabolites · 2022Article
- The structural, dynamic, and thermodynamic basis of darunavir resistance of a heavily mutated HIV-1 protease using molecular dynamics simulation.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-resistance-associated mutation in essential proteins of the viral life cycle is a major concern in anti-retroviral therapy. M46I, a non-active site mutation in HIV-1 protease has been clinically associated with saquinavir resistance in HIV patients. A 100 ns molecular dynamics (MD) simulation and MM-PBSA calculations were performed to study the molecular mechanism of M46I-mutation-based saquinavir resistance. In order to acquire deeper insight into the drug-resistance mechanism, the flap curling, closed/semi-open/open conformations, and active site compactness were studied. The M46I mutation significantly affects the energetics and conformational stability of HIV-1 protease in terms of RMSD, RMSF, Rg, SASA, and hydrogen formation potential. This mutation significantly decreased van der Waals interaction and binding free energy (∆G) in the M46I-saquinavir complex and induced inward flap curling and a wider opening of the flaps for most of the MD simulation period. The predominant open conformation was reduced, but inward flap curling/active site compactness was increased in the presence of saquinavir in M46I HIV-1 protease. In conclusion, the M46I mutation induced structural dynamics changes that weaken the protease grip on saquinavir without distorting the active site of the protein. The produced information may be utilized for the discovery of inhibitor(s) against drug-resistant HIV-1 protease.
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