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