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Receptor‐Dependent 4D‐QSAR Analysis of Peptidemimetic Inhibitors of Trypanosoma cruzi Trypanothione Reductase with Receptor‐Based Alignment
Author(s) -
da Rocha Pita Samuel Silva,
Albuquerque Magaly Girão,
Rodrigues Carlos Rangel,
Castro Helena Carla,
Hopfinger Anton J.
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01338.x
Subject(s) - quantitative structure–activity relationship , chemistry , stereochemistry , trypanosoma cruzi , ligand (biochemistry) , computational biology , biology , biochemistry , receptor , computer science , parasite hosting , world wide web
Receptor‐dependent four‐dimensional quantitative structure–activity relationship (RD‐4D‐QSAR) studies were applied on a series of 21 peptides reversible inhibitors of Trypanosoma cruzi trypanothione reductase (TR) (Amino Acids, 20, 2001, 145). The RD‐4D‐QSAR (J Chem Inform Comp Sci, 43, 2003, 1591) approach can evaluate multiple conformations from molecular dynamics simulation and several superposition structure alignments inside a box composed by unitary cubic cells. The descriptors are the occupancy frequency of the atoms types inside the grid cells. We could develop 3D‐QSAR models that were highly predictive ( q 2 above 0.71). The 3D‐QSAR models can be visualized as a spatial map of atom types that are important on the comprehension of the ligand–enzyme interaction mechanism, pointing main pharmacophoric groups and TR subsites described in the literature. We were able also to identify some TR subsites for further development in the drug discovery process against tropical diseases not yet studied.