A fragment-based approach for ligand binding affinity and selectivity for the liver X receptor beta


Autoria(s): Salum, Lívia de Barros; Andricopulo, Adriano Defini; Honorio, Káthia Maria
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

06/11/2013

06/11/2013

2012

Resumo

Selective modulation of liver X receptor beta (LXR beta) has been recognized as an important approach to prevent or reverse the atherosclerotic process. In the present work, we have developed robust conformation-independent fragment-based quantitative structure-activity and structure-selectivity relationship models for a series of quinolines and cinnolines as potent modulators of the two LXR sub-types. The generated models were then used to predict the potency of an external test set and the predicted values were in good agreement with the experimental results, indicating the potential of the models for untested compounds. The final 2D molecular recognition patterns obtained were integrated to 3D structure-based molecular modeling studies to provide useful insights into the chemical and structural determinants for increased LXR beta binding affinity and selectivity. (C) 2011 Elsevier Inc. All rights reserved.

FAPESP (The State of Sao Paulo Research Foundation)

FAPESP (The State of Sao Paulo Research Foundation)

CNPq (The National Council for Scientific and Technological Development)

CNPq (The National Council for Scientific and Technological Development)

CAPES (Coordination for the Improvement of High Education Personnel), Brazil

CAPES (Coordination for the Improvement of High Education Personnel), Brazil

Identificador

Journal of Molecular Graphics and Modelling, New York, v. 32, n. 2, supl. 1, Part 1, pp. 19-31, feb, 2012

1093-3263

http://www.producao.usp.br/handle/BDPI/42486

10.1016/j.jmgm.2011.09.007

http://dx.doi.org/10.1016/j.jmgm.2011.09.007

Idioma(s)

eng

Publicador

Elsevier Science INC

New York

Relação

Journal of Molecular Graphics and Modelling

Direitos

closedAccess

Copyright ELSEVIER SCIENCE INC

Palavras-Chave #Binding Affinity #Drug Design #Fragment-Based Analysis #LXR BETA #Selectivity #Acid Based Quinolines #Drug Design #QSAR #LXR #Modulators #Atherosclerosis #Agonists #Disease #Series #Biochemical Research Methods #Biochemistry & Molecular Biology #Computer Science, Interdisciplinary Applications #Crystallography #Mathematical & Computational Biology
Tipo

article

original article

publishedVersion