Profiling the Interaction Mechanism of Quinoline/Quinazoline Derivatives as MCHR1 Antagonists: An in Silico Method

International Journal of Molecular Sciences

Mingwei Wu²  Yan Li²  Xinmei Fu¹  Jinghui Wang²  Shuwei Zhang² 

[1] State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China; E-Mail:;Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Dalian University of Technology, Dalian 116024, China; E-Mails:

关键词: MCHR1;    3D-QSAR;    molecular docking;    MD simulation;   

DOI  :  10.3390/ijms150915475

来源: mdpi

【 摘 要 】

Melanin concentrating hormone receptor 1 (MCHR1), a crucial regulator of energy homeostasis involved in the control of feeding and energy metabolism, is a promising target for treatment of obesity. In the present work, the up-to-date largest set of 181 quinoline/quinazoline derivatives as MCHR1 antagonists was subjected to both ligand- and receptor-based three-dimensional quantitative structure–activity (3D-QSAR) analysis applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The optimal predictable CoMSIA model exhibited significant validity with the cross-validated correlation coefficient (Q²) = 0.509, non-cross-validated correlation coefficient (R²_ncv) = 0.841 and the predicted correlation coefficient (R²_pred) = 0.745. In addition, docking studies and molecular dynamics (MD) simulations were carried out for further elucidation of the binding modes of MCHR1 antagonists. MD simulations in both water and lipid bilayer systems were performed. We hope that the obtained models and information may help to provide an insight into the interaction mechanism of MCHR1 antagonists and facilitate the design and optimization of novel antagonists as anti-obesity agents.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.