Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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Structural Aspects of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibition

Author(s): Anton Beyer, Luckhana Lawtrakul, Pornpan Pungpo, Peter Wolschann.

Abstract:

HIV-1 Reverse transcriptase (RT) is an essential enzyme for HIV-1 replication and, therefore, it is an important target for the attack of antiviral agents. Although some products are already on the market, there is need to design new drugs, because mutation in drug interacting disease proteins decreases the efficiency of the existing drugs. Non-nucleoside RT inhibitors fill up an allosteric, mainly hydrophobic pocket in a distinct distance from the enzymes active center. X-ray crystallographic investigations on the enzyme and on enzyme complexes provide information about the structural consequences of the protein-inhibitor interaction. Applying molecular simulations the dynamic behaviour of these biomolecular systems can be obtained in order to get some insight into the molecular flexibilities and into the detailed inhibition mechanism. Amino acids which are important for the inhibition mechanism and the interaction with inhibitor molecules can be identified for further considerations with more accurate molecular calculations. QSAR studies allow the development of proper prediction models, which are used to design new drugs. Combination of molecular docking, energy minimization and MD or MC calculations with various QSAR methods will support screening methods to find new lead compounds.

Keywords: HIV-1 reverse transcriptase, Non-nucleoside reverse transcriptase inhibitor, X-ray structures, quantitative structureactivity analysis, molecular simulation

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Article Details

VOLUME: 3
ISSUE: 2
Year: 2007
Page: [87 - 100]
Pages: 14
DOI: 10.2174/157340907780809507
Price: $58