title: Virtual screening studies on HIV-1 reverse transcriptase inhibitors to design potent leads.
abstract: The purpose of this study is to identify novel and potent inhibitors against HIV-1 reverse transcriptase (RT). The crystal structure of the most active ligand was converted into a feature-shaped query. This query was used to align molecules to generate statistically valid 3D-QSAR (r(2) = 0.873) and Pharmacophore models (HypoGen). The best HypoGen model consists of three Pharmacophore features (one hydrogen bond acceptor, one hydrophobic aliphatic and one ring aromatic) and further validated using known RT inhibitors. The designed novel inhibitors are further subjected to docking studies to reduce the number of false positives. We have identified and proposed some novel and potential lead molecules as reverse transcriptase inhibitors using analog and structure based studies.
authors.affiliation: Informatics, GVK Biosciences Private Limited, 37 Sterling Road, Chennai 600034, Tamil Nadu, India. vadivelan@gvkbio.com
authors.forename: S
authors.initials: S
authors.lastname: Vadivelan
authors.forename: T N
authors.initials: TN
authors.lastname: Deeksha
authors.forename: S
authors.initials: S
authors.lastname: Arun
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Machiraju
authors.forename: Rambabu
authors.initials: R
authors.lastname: Gundla
authors.forename: Barij Nayan
authors.initials: BN
authors.lastname: Sinha
authors.forename: Sarma A R P
authors.initials: SA
authors.lastname: Jagarlapudi
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D008024:Ligands; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase