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Author(s): Catia Teixeira
Jose R B Gomes
Thierry Couesnon
Paula Gomes
Title: Molecular docking and 3D-quantitative structure activity relationship analyses of peptidyl vinyl sulfones: Plasmodium Falciparum cysteine proteases inhibitors
Issue Date: 2011
Abstract: Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure- activity relationship (3D-QSAR) studies were conducted on a series (39 molecules) of peptidyl vinyl sulfone derivatives as potential Plasmodium Falciparum cysteine proteases inhibitors. Two different methods of alignment were employed: (i) a receptor-docked alignment derived from the structure-based docking algorithm GOLD and (ii) a ligand-based alignment using the structure of one of the ligands derived from a crystal structure from the PDB databank. The best predictions were obtained for the receptor-docked alignment with a CoMFA standard model (q(2) = 0.696 and r(2) = 0.980) and with CoMSIA combined electrostatic, and hydrophobic fields (q(2) = 0.711 and r(2) = 0.992). Both models were validated by a test set of nine compounds and gave satisfactory predictive r(2) pred values of 0.76 and 0.74, respectively. CoMFA and CoMSIA contour maps were used to identify critical regions where any change in the steric, electrostatic, and hydrophobic fields may affect the inhibitory activity, and to highlight the key structural features required for biological activity. Moreover, the results obtained from 3D-QSAR analyses were superimposed on the Plasmodium Falciparum cysteine proteases active site and the main interactions were studied. The present work provides extremely useful guidelines for future structural modifications of this class of compounds towards the development of superior antimalarials.
Subject: Ciências da computação e da informação
Computer and information sciences
Scientific areas: Ciências exactas e naturais::Ciências da computação e da informação
Natural sciences::Computer and information sciences
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FCUP - Artigo em Revista Científica Internacional

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