ArticleAntimicrobial agents and chemotherapy2012
Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Analysis of raltegravir analogs to enhance inhibitory efficiency against HIV integrase.Scientific reports · 2025Article
- Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of theMolecules (Basel, Switzerland) · 2023Article
- Article
- Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Review
- Cellulose Acetate Phthalate and Antiretroviral Nanoparticle Fabrications for HIV Pre-Exposure Prophylaxis.Polymers · 2017Article
- Impact of Genetic Variations in HIV-1 Tat on LTR-Mediated Transcription via TAR RNA Interaction.Frontiers in microbiology · 2017Article
- Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site.Nucleic acids research · 2016Article
- Comparison of Newly Assembled Full Length HIV-1 Integrase With Prototype Foamy Virus Integrase: Structure-Function Prospective.Jundishapur journal of microbiology · 2016Article
- 6,7-Dihydroxyisoindolin-1-one and 7,8-Dihydroxy-3,4-Dihydroisoquinolin- 1(2H)-one Based HIV-1 Integrase Inhibitors.Current topics in medicinal chemistry · 2016Review
- Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data.Bioinformation · 2016Article
- In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1.Journal of biomedical research · 2015Article
- Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase.Antimicrobial agents and chemotherapy · 2013Article
- Computational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studied.Journal of molecular modeling · 2013Article
- A homology model of HIV-1 integrase and analysis of mutations designed to test the model.Journal of molecular biology · 2013Article
- Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase.ACS chemical biology · 2013Article
- HIV integrase inhibitors: 20-year landmark and challenges.Advances in pharmacology (San Diego, Calif.) · 2013Review
- Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors.Acta naturae · 2013Article
- Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.PloS one · 2013Article
- Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer.Bioinformation · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The design of novel integrase (IN) inhibitors has been aided by recent crystal structures revealing the binding mode of these compounds with a full-length prototype foamy virus (PFV) IN and synthetic viral DNA ends. Earlier docking studies relied on incomplete structures and did not include the contribution of the viral DNA to inhibitor binding. Using the structure of PFV IN as the starting point, we generated a model of the corresponding HIV-1 complex and developed a molecular dynamics (MD)-based approach that correlates with the in vitro activities of novel compounds. Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data. Three additional compounds were docked into the IN-DNA complex model and subjected to MD simulations. All three gave interaction potentials within 1 standard deviation of values estimated from the training set, and the most active compound was identified. Additional MD analysis of the raltegravir- and dolutegravir-bound complexes gave internal and interaction energy values that closely match the experimental binding energy of a compound related to raltegravir that has similar activity. These approaches can be used to gain a deeper understanding of the interactions of the inhibitors with the HIV-1 intasome and to identify promising scaffolds for novel integrase inhibitors, in particular, compounds that retain activity against a range of drug-resistant mutants, making it possible to streamline synthesis and testing.
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