Dockinig Study and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Analyses of Transforming Growth Factor-beta Type I Receptor Kinase Inhibitors

作者：Yang Min^*; Zhou Lu; Zuo Zhili; Mancera Ricardo; Song Hang; Tang Xiangyang; Ma Xiang

来源：QSAR and Combinatorial Science, 2009, 28(11-12): 1300-1308.

DOI：10.1002/qsar.200960015

• 3D-QSAR
• Gold
• CoMFA
• TGF-beta RI
• Medicinal chemistry
• Structure-property relationships

Transforming growth factor-beta Type I Receptor Kinase (TGF-beta RI) is an important and novel drug target for the treatment of fibrosis and cancer. In this study, docking and comparative molecular field analysis (CoMFA) were performed and the structural characteristics of TGF-beta RI ligands were rationalized. The genetic algorithm search method in the docking program GOLD 3.0.1 was employed to determine the likely binding mode conformations of 70 inhibitors in the active site of TGF-beta RI. Based on the binding mode conformations, a highly predictive 3D-QSAR model was developed with a q(2) value of 0.589 for CoMFA. The predictive ability of this model was validated with a number of compounds that were not included in the original training set. Furthermore, the 3D-QSAR model was mapped back to the binding site of the TGF-beta RI to obtain a better understanding of the essential interactions between the inhibitors and TGF-beta RI. The robustness, predictive ability and automated alignment generation of this model make it a potential tool for the design and development of new drug leads to inhibit TGF-beta RI.

• 出版日期2009-12
• 单位四川大学