ArticleJournal of molecular modeling2007
Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations.
Article in Journal of molecular modeling, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 50 citations in OpenAlex.
- Integrative Computational Approaches for Understanding Drug Resistance in HIV-1 Protease Subtype C.Viruses · 2025Review
- Premature Activation of the HIV-1 Protease Is Influenced by Polymorphisms in the Hinge Region.Viruses · 2024Article
- HIV-1 protease with 10 lopinavir and darunavir resistance mutations exhibits altered inhibition, structural rearrangements and extreme dynamics.Journal of molecular graphics & modelling · 2022Article
- Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022Article
- Drug resistance mutations in protease gene of HIV-1 subtype C infected patient population.Virusdisease · 2021Article
- Article
- Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease.BMC bioinformatics · 2015Article
- Structural basis for the recognition of human cytomegalovirus glycoprotein B by a neutralizing human antibody.PLoS pathogens · 2014Article
- The role of select subtype polymorphisms on HIV-1 protease conformational sampling and dynamics.The Journal of biological chemistry · 2014Article
- Mutations in herpes simplex virus gD protein affect receptor binding by different molecular mechanisms.Journal of molecular modeling · 2014Article
- Inhibitor-induced conformational shifts and ligand-exchange dynamics for HIV-1 protease measured by pulsed EPR and NMR spectroscopy.The journal of physical chemistry. B · 2012Article
- HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements.Biochemistry · 2012Article
- A comparative study of HIV-1 and HTLV-I protease structure and dynamics reveals a conserved residue interaction network.Journal of molecular modeling · 2011Article
- Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease.Journal of molecular modeling · 2010Article
- Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant.Journal of molecular modeling · 2007Article
- Dual selection pressure by drugs and HLA class I-restricted immune responses on human immunodeficiency virus type 1 protease.Journal of virology · 2007Article
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4 authors at 1 institution in 1 country.
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Abstract
Drug resistance is a very important factor contributing to the failure of current HIV therapies. The ability to understand the resistance mechanism of HIV-protease mutants may be useful in developing more effective and longer lasting treatment regimens. In this paper, we report the first computational study of the clinically relevant E35D mutation of HIV-1 protease in its unbound conformation and complexed with the clinical inhibitor amprenavir and a sample substrate (Thr-Ile-Met-Met-Gln-Arg). Our data, collected from 10 ns molecular-dynamics simulations, show that the E35D mutation results in an increased flexibility of the flaps, thereby affecting the conformational equilibrium between the closed and semi-open conformations of the free protease. The E35D mutation also causes a significant reduction of the calculated binding free energies both for substrate and amprenavir, thus giving a plausible explanation for its ability to increase the level of resistance. One possible explanation for the emergence of this mutation, despite its unfavorable effect on substrate affinity, might be the role of E35D as an escape mutation, which favors escape from the immune system in addition to conferring drug resistance.
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