Computational development of rubromycin-based lead compounds for HIV-1 reverse transcriptase inhibition

Carlos E P Bernardo; Pedro J Silva

doi:10.7717/peerj.470

Computational development of rubromycin-based lead compounds for HIV-1 reverse transcriptase inhibition

PeerJ. 2014 Jul 10:2:e470. doi: 10.7717/peerj.470. eCollection 2014.

Authors

Carlos E P Bernardo¹, Pedro J Silva¹

Affiliation

¹ REQUIMTE/Faculdade de Ciências da Saúde, Universidade Fernando Pessoa , Rua Carlos da Maia, Porto , Portugal.

Abstract

The binding of several rubromycin-based ligands to HIV1-reverse transcriptase was analyzed using molecular docking and molecular dynamics simulations. MM-PBSA analysis and examination of the trajectories allowed the identification of several promising compounds with predicted high affinity towards reverse transcriptase mutants which have proven resistant to current drugs. Important insights on the complex interplay of factors determining the ability of ligands to selectively target each mutant have been obtained.

Keywords: Computer-aided drug design; Docking; Molecular dynamics.

Grants and funding

Research at REQUIMTE is supported by Fundação para a Ciência e a Tecnologia through grant no. PEst-C/EQB/LA0006/2011. This work has been financed by FEDER through Programa Operacional Factores de Competitividade–COMPETE and by Portuguese Funds through FCT–Fundação para a Ciência e a Tecnologia under project PTDC/QUI-QUI/111288/2009. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.