Next Article in Journal
Three Peptides from Soy Glycinin Modulate Glucose Metabolism in Human Hepatic HepG2 Cells
Next Article in Special Issue
Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors
Previous Article in Journal
A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats
Previous Article in Special Issue
From Genome to Structure and Back Again: A Family Portrait of the Transcarbamylases
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(11), 27350-27361; doi:10.3390/ijms161126026

An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors

1
Department of Chemistry, Yunnan University, Kunming 650091, China
2
Department of Chemistry, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Christo Z. Christov
Received: 26 September 2015 / Revised: 31 October 2015 / Accepted: 6 November 2015 / Published: 16 November 2015
View Full-Text   |   Download PDF [2428 KB, uploaded 16 November 2015]   |  

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. View Full-Text
Keywords: imidazopyridine; B-Raf kinase; molecular docking; molecular dynamic simulation imidazopyridine; B-Raf kinase; molecular docking; molecular dynamic simulation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Xie, H.; Li, Y.; Yu, F.; Xie, X.; Qiu, K.; Fu, J. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors. Int. J. Mol. Sci. 2015, 16, 27350-27361.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top