基于对接的 PPARγ 全激动剂 3D-QSAR 模型的开发。

Development of docking-based 3D-QSAR models for PPARgamma full agonists.

机构信息

Grup de Recerca en Nutrigenòmica, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, C/ Marcel. lí Domingo s/n, 43007 Tarragona, Catalonia, Spain.

出版信息

J Mol Graph Model. 2012 Jun;36:1-9. doi: 10.1016/j.jmgm.2012.03.001. Epub 2012 Mar 14.

DOI:10.1016/j.jmgm.2012.03.001

PMID:22503857

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) has become an attractive molecular target for drugs that aim to treat diabetes mellitus type II, and its therapeutic potency against skin cancer and other skin diseases is also currently being explored. To study the relationship between the structure of several PPARγ full agonists and the trans-activation activity of PPARγ, we have performed a three-dimensional quantitative structure-activity relationship (3D-QSAR) study of tyrosine-based derivatives, based on the 3D alignment of conformations obtained by docking. Highly predictive 3D-QSAR models, with Pearson-R values of 0.86 and 0.90, were obtained for the transactivation activity and binding affinity of PPARγ, respectively. These models are in good agreement with the structural characteristics of the binding pocket of PPARγ and provide some structural insights for the improvement of PPARγ full agonist bioactivities.

摘要

过氧化物酶体增殖物激活受体γ（PPARγ）已成为治疗 II 型糖尿病的药物的一个有吸引力的分子靶标，其治疗皮肤癌和其他皮肤病的功效也正在被探索。为了研究几种 PPARγ 完全激动剂的结构与 PPARγ 的反式激活活性之间的关系，我们对酪氨酸衍生物进行了三维定量构效关系（3D-QSAR）研究，该研究基于通过对接获得的构象的三维排列。对于 PPARγ 的反式激活活性和结合亲和力，分别获得了具有高预测性的 3D-QSAR 模型，Pearson-R 值分别为 0.86 和 0.90。这些模型与 PPARγ 的结合口袋的结构特征非常吻合，并为提高 PPARγ 完全激动剂的生物活性提供了一些结构见解。