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Proposal of a new binding orientation for non-peptide AT1 antagonists: homology modeling, docking and three-dimensional quantitative structure-activity relationship analysis.

Abstract：

:A three-dimensional model of the AT1 receptor was constructed by means of a homology modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template and taking into account the available site-directed mutagenesis data. The docking of losartan and its active metabolite EXP3174, followed by 1 ns of molecular dynamics (MD) simulation inserted into the phospholipid bilayer, suggested a different binding orientation for these antagonists from those previously proposed. Furthermore, the docking of several non-peptide antagonists was used as an alignment tool for the development of a three-dimensional quantitative structure-activity relationship (3D-QSAR) model, and the good results confirmed our binding hypothesis and the reliability of the model.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Tuccinardi T,Calderone V,Rapposelli S,Martinelli A

doi

10.1021/jm060338p

subject

Has Abstract

pub_date

2006-07-13 00:00:00

pages

4305-16

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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