Abstract
A Hybrid pharmacophore and structure-based drug design approach, aided by binding mode analysis, molecular dynamics simulations and per-residue energy contribution calculations, was used to design five novel structural scaffolds as potential bifunctional anti-HIV/TB inhibitors. Binding free energy calculations demonstrated that the proposed compounds exhibited better binding affinities towards HIV PR and BlaC enzymes when compared to prototype drugs, darunavir and meropenem, respectively. The lead design strategy presented in this work could serve as a useful tool for developing bifunctional inhibitors against wide range of biological targets.
Keywords: Dual acting HIV/TB inhibitors, HIV-1 protease inhibitors, B-lactamase inhibitors, TB, computer-aided drug design, Bifunctional inhibitors.
Letters in Drug Design & Discovery
Title:Bifunctional Anti-HIV/TB Inhibitors: Perspective from In-Silico Design and Molecular Dynamics Simulations
Volume: 10 Issue: 8
Author(s): Lauren Blake and Mahmoud E. S. Soliman
Affiliation:
Keywords: Dual acting HIV/TB inhibitors, HIV-1 protease inhibitors, B-lactamase inhibitors, TB, computer-aided drug design, Bifunctional inhibitors.
Abstract: A Hybrid pharmacophore and structure-based drug design approach, aided by binding mode analysis, molecular dynamics simulations and per-residue energy contribution calculations, was used to design five novel structural scaffolds as potential bifunctional anti-HIV/TB inhibitors. Binding free energy calculations demonstrated that the proposed compounds exhibited better binding affinities towards HIV PR and BlaC enzymes when compared to prototype drugs, darunavir and meropenem, respectively. The lead design strategy presented in this work could serve as a useful tool for developing bifunctional inhibitors against wide range of biological targets.
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Cite this article as:
Blake Lauren and Soliman E. S. Mahmoud, Bifunctional Anti-HIV/TB Inhibitors: Perspective from In-Silico Design and Molecular Dynamics Simulations, Letters in Drug Design & Discovery 2013; 10 (8) . https://dx.doi.org/10.2174/15701808113109990023
DOI https://dx.doi.org/10.2174/15701808113109990023 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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