Comprehensive Model of Wild-type and Mutant HIV-1 Reverse Transciptases

Overview

Journal J Comput Aided Mol Des

Publisher Springer

Specialties Biomedical Engineering
Molecular Biology

Date 2012 Jul 27

PMID 22833004

Citations 4

Authors

Flavio Ballante

Ira Musmuca

Garland R Marshall

Rino Ragno

Affiliations

Soon will be listed here.

Abstract

An enhanced version of COMBINE that uses both ligand-based and structure-based alignment of ligands has been used to build a comprehensive 3-D QSAR model of wild-type HIV-1 reverse transcriptase and drug-resistant mutants. The COMBINEr model focused on 7 different RT enzymes complexed with just two HIV-RT inhibitors, niverapine (NVP) and efavirenz (EFV); therefore, 14 inhibitor/enzyme complexes comprised the training set. An external test set of chiral 2-(alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones (DABOs) was used to test predictability. The COMBINEr model MC4, although developed using only two inhibitors, predicted the experimental activities of the test set with an acceptable average absolute error of prediction (0.89 pK (i)). Most notably, the model was able to correctly predict the right eudismic ratio for two R/S pairs of DABO derivatives. The enhanced COMBINEr approach was developed using only software freely available to academics.

Citing Articles

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Ligand-based and structure-based studies to develop predictive models for SARS-CoV-2 main protease inhibitors through the 3d-qsar.com portal.

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