title: Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.
abstract: Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.
authors.affiliation: Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Lucianna Helene
authors.initials: LH
authors.lastname: Santos
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Rafaela Salgado
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Ernesto Raúl
authors.initials: ER
authors.lastname: Caffarena
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D017076:Computer-Aided Design; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase