ArticleJournal of molecular biology2008
Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 101 citations in OpenAlex.
- Designing Potent HIV‑1 Protease Inhibitors Using Machine Learning and QSAR Approaches.ACS omega · 2025Article
- Predicting the Impact of Drug Resistance Mutations on Inhibitor Potency with Molecular Dynamics and Machine Learning.The journal of physical chemistry. B · 2025Article
- Predicting Affinity Through Homology (PATH): Interpretable binding affinity prediction with persistent homology.PLoS computational biology · 2025Article
- Design, Synthesis, and Biological Evaluation of Darunavir Analogs as HIV-1 Protease Inhibitors.ACS bio & med chem Au · 2024Article
- Identification of steroidal cardenolides from Calotropis procera as novel HIV-1 PR inhibitors: A molecular docking & molecular dynamics simulation study.The Indian journal of medical research · 2024Article
- FMO-guided design of darunavir analogs as HIV-1 protease inhibitors.Scientific reports · 2024Article
- Prediction of protein-ligand binding affinity via deep learning models.Briefings in bioinformatics · 2024Review
- Integrative modeling of diverse protein-peptide systems using CABS-dock.PLoS computational biology · 2023Article
- A topological data analytic approach for discovering biophysical signatures in protein dynamics.PLoS computational biology · 2022Article
- Article
- Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17.Journal of molecular graphics & modelling · 2021Article
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Article
- Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations.The FEBS journal · 2020Article
- Impacts of drug resistance mutations on the structural asymmetry of the HIV-2 protease.BMC molecular and cell biology · 2020Article
- Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.Biochemical and biophysical research communications · 2019Article
- Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues.ACS omega · 2019Article
- Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein.FEBS open bio · 2018Article
- Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K.Journal of medicinal chemistry · 2017Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 (human immunodeficiency virus type 1) protease (PR) and its mutants are important antiviral drug targets. The PR flap region is critical for binding substrates or inhibitors and catalytic activity. Hence, mutations of flap residues frequently contribute to reduced susceptibility to PR inhibitors in drug-resistant HIV. Structural and kinetic analyses were used to investigate the role of flap residues Gly48, Ile50, and Ile54 in the development of drug resistance. The crystal structures of flap mutants PR(I50V) (PR with I50V mutation), PR(I54V) (PR with I54V mutation), and PR(I54M) (PR with I54M mutation) complexed with saquinavir (SQV) as well as PR(G48V) (PR with G48V mutation), PR(I54V), and PR(I54M) complexed with darunavir (DRV) were determined at resolutions of 1.05-1.40 A. The PR mutants showed changes in flap conformation, interactions with adjacent residues, inhibitor binding, and the conformation of the 80s loop relative to the wild-type PR. The PR contacts with DRV were closer in PR(G48V)-DRV than in the wild-type PR-DRV, whereas they were longer in PR(I54M)-DRV. The relative inhibition of PR(I54V) and that of PR(I54M) were similar for SQV and DRV. PR(G48V) was about twofold less susceptible to SQV than to DRV, whereas the opposite was observed for PR(I50V). The observed inhibition was in agreement with the association of G48V and I50V with clinical resistance to SQV and DRV, respectively. This analysis of structural and kinetic effects of the mutants will assist in the development of more effective inhibitors for drug-resistant HIV.
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