title: An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.
abstract: In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.
authors.affiliation: Department of Chemistry, Yunnan University, Kunming 650091, China. front701228.student@sina.com.|Department of Chemistry, School of Pharmaceutical Science &amp; Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. front701228.student@sina.com.
authors.forename: Huiding
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science &amp; Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. liyupeng26@126.com.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science &amp; Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. yufang519@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Yunnan University, Kunming 650091, China. xgxie@ynu.edu.cn.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science &amp; Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. chenneyao16@hotmail.com.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Qiu
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science &amp; Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China. Fujj920@163.com.
authors.forename: Jijun
authors.initials: J
authors.lastname: Fu
mesh_terms: D001665:Binding Sites; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048493:Proto-Oncogene Proteins B-raf
keywords: B-Raf kinase; imidazopyridine; molecular docking; molecular dynamic simulation