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Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase
Marina Udier-Blagović1, Edward K Watkins, Julian Tirado-Rives
1Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
Abstract:
Monte Carlo-extended linear response (MC/ELR) calculations are used to examine the binding of efavirenz analogues with the K103N mutant of HIV-1 reverse transcriptase (HIVRT). A regression equation previously reported for the wild type (WT) enzyme is shown to predict 47 experimental activities for the K103N mutant with a q(2)=0.55 and avg error of only 0.46 kcal/mol. Further analysis identifies the key features for binding to the K103N mutant: ligand flexibility, burial of hydrophobic surface area, and protein-ligand van der Waals interactions.
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