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Type: Artigo de periódico
Title: Comparative chemometric and QSAR/SAR study of structurally unrelated substrates of a MATE efflux pump VmrA from V. parahaemolyticus: Prediction of multidrug resistance
Author: Kiralj, R
Ferreira, MMC
Abstract: Structures of 12 structurally unrelated agents (training set) and 19 diverse agents (prediction set) were modeled at the PM3 level and the molecular descriptors obtained were correlated with pMIC (pMIC = - log(MIC/mol/dm(3)) values for E coli strains KAM32 (without VmrA efflux pump) and KAM32/pVCJ6 (with VmrA). Partial Least Squares (PLS) and Principal Component Regression (PCR) models were built and used to predict pMICs. Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) were performed for training and training + prediction sets. Agent-receptor interaction descriptors were calculated for complexes with these or the most similar agents, as retrieved from the Protein Data Bank (PDB). Good substrates of VmrA from Vibrio parahaemolyticus AQ3334 are nonlinear, rigid, and condensed hetero-aromatics, rather hydrophobic, involved in aromatic-aromatic, hydrophobic- hydrophobic, hydrophobic - hydrophilic, and hydrogen bond contacts with VmrA. Qualitative and quantitative structure-activity relationships [(Q)SARs] predicted well the resistance/ sensitivity of VmrA to 19 agents. This can have practical application in assays with V parahaemolyticus and other noncholera Vibrio spp. Agent-receptor interaction descriptors correlate with experimental and predicted pMICs, giving a new insight into possible VmrA-mediated agent efflux mechanisms.
Subject: agent-receptor interactions
molecular descriptors
multidrug resistance
regression models
semiempirical methods
Country: Alemanha
Editor: Wiley-v C H Verlag Gmbh
Citation: Qsar & Combinatorial Science. Wiley-v C H Verlag Gmbh, v. 27, n. 3, n. 314, n. 329, 2008.
Rights: fechado
Identifier DOI: 10.1002/qsar.200630164
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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