کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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377965 | 658857 | 2009 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Computational proteomics analysis of binding mechanisms and molecular signatures of the HIV-1 protease drugs Computational proteomics analysis of binding mechanisms and molecular signatures of the HIV-1 protease drugs](/preview/png/377965.png)
SummaryObjectiveComputational proteomics analysis of biomolecular interactions is proposed to determine molecular signatures of the HIV-1 protease inhibitors. A comparative microscopic analysis is conducted for a panel of inhibitors which exemplify a diversity of the HIV-1 PR binding mechanisms, from the active site inhibition to intervening with the protease folding and dimerization.Methods and materialsReplica-exchange Monte Carlo simulations with the conformational ensembles of the HIV-1 PR dimer and monomer structures enable a molecular analysis underlying diversity of the HIV-1 PR binding mechanisms.ResultsWe have investigated the molecular basis underlying diversity of the HIV-1 PR binding mechanisms. The molecular basis of the HIV-1 PR active site and dimerization inhibition mechanisms has been analyzed for an active site tripeptide inhibitor and a tetrapeptide inhibitor, which can act as both a dimerization inhibitor and a competitive active site inhibitor. We have also simulated a structural mimicry mechanism of the HIV-1 PR folding inhibition and dimerization, according to which the folding inhibitor targets the conserved HIV-1 PR regions by mimicking the interaction network of the active dimer.ConclusionsWe have shown that binding interfaces of the studied dimerization and folding HIV-1 PR inhibitors may enable structural mimicry with the hot spot residues of the HIV-1 PR dimer. The proposed structural models of intervening with the HIV-1 PR dimerization and folding support the mechanism of structural mimicry, which may alleviate drug resistance effects.
Journal: Artificial Intelligence in Medicine - Volume 45, Issues 2–3, February–March 2009, Pages 197–206