title: Docking and multivariate methods to explore HIV-1 drug-resistance: a comparative analysis.
abstract: In this paper we describe a comparative analysis between multivariate and docking methods in the study of the drug resistance to the reverse transcriptase and the protease inhibitors. In our early papers we developed a simple but efficient method to evaluate the features of compounds that are less likely to trigger resistance or are effective against mutant HIV strains, using the multivariate statistical procedures PCA and DA. In the attempt to create a more solid background for the prediction of susceptibility or resistance, we carried out a comparative analysis between our previous multivariate approach and molecular docking study. The intent of this paper is not only to find further support to the results obtained by the combined use of PCA and DA, but also to evidence the structural features, in terms of molecular descriptors, similarity, and energetic contributions, derived from docking, which can account for the arising of drug-resistance against mutant strains.
authors.affiliation: Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo, Italy. almerico@unipa.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.forename: Marco
authors.initials: M
authors.lastname: Tutone
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D017076:Computer-Aided Design; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000235:genetics; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015999:Multivariate Analysis; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D008024:Ligands; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1