Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/52865
Type: Artigo de periódico
Title: LQTA-QSAR: A New 4D-QSAR Methodology
Author: Martins, JPA
Barbosa, EG
Pasqualoto, KFM
Ferreira, MMC
Abstract: A novel 4D-QSAR approach which makes use of the molecular dynamics (MD) trajectories and topology information retrieved from the GROMACS package is presented in this study. This new methodology, named LQTA-QSAR (LQTA, Laboratorio de Quimiometria Teorica e Aplicada), has a module (LQTAgrid) that calculates intermolecular interaction energies at each grid point considering probes and all aligned conformations resulting from MD simulations. These interaction energies are the independent variables or descriptors employed in a QSAR analysis. The comparison of the proposed methodology to other 4D-QSAR and CoMFA formalisms was performed using a set of forty-seven glycogen phosphorylase b inhibitors (data set 1) and a set of forty-four MAP p38 kinase inhibitors (data set 2). The QSAR models for both data sets were built using the ordered predictor selection (OPS) algorithm for variable selection. Model validation was carried out applying y-randomization and leave-N-out cross-validation in addition to the external validation. PLS models for data set I and 2 provided the following statistics: q(2) = 0.72, r(2) = 0.81 for 12 variables selected and 2 latent variables and q(2) = 0.82, r(2) = 0.90 for 10 variables selected and 5 latent variables, respectively. Visualization of the descriptors in 3D space was successfully interpreted from the chemical point of view, supporting the applicability of this new approach in rational drug design.
Country: EUA
Editor: Amer Chemical Soc
Rights: fechado
Identifier DOI: 10.1021/ci900014f
Date Issue: 2009
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

Files in This Item:
File Description SizeFormat 
WOS000267394300011.pdf398.94 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.