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Journal of Chemistry
Volume 2015, Article ID 879238, 13 pages
http://dx.doi.org/10.1155/2015/879238
Research Article

Study on Molecular Recognition between Euphorbia Factor L713283 and β-Tubulin via Molecular Simulation Methods

1Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, China
2Chongqing High-Tech Industrial Development Zone, Chongqing 400039, China
3Faculty of Biotechnology Industry, Chengdu University, Chengdu 610106, China
4College of Chemistry, Leshan Normal University, Leshan 614004, China

Received 26 August 2015; Revised 25 October 2015; Accepted 28 October 2015

Academic Editor: Teodorico C. Ramalho

Copyright © 2015 Shan Chang et al. 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.

Abstract

Euphorbia factor L713283 is a new lathyrane diterpene isolated from Euphorbia lathyris and shows strong anticancer activity. By using molecular similarity analysis, β-tubulin was identified as one of the possible targets of L713283. We further investigated the binding modes of L713283 with β-tubulin using molecular docking and molecular dynamics (MD) simulation methods. The results indicated that the binding site between β-tubulin and L713283 was composed of the four regions, that is, residues Phe20~Glu27, Leu225~Thr232, Phe270~Gly277, and Ile356~Met363. MM/GBSA method was used to calculate the binding free energy and determine the key residues for the association of L713283 with β-tubulin. It was found that nonpolar interactions made the major contributions for the binding. In addition, we compared the binding pocket and motion modes of L713283-free and L713283-bound β-tubulin systems. It is proposed that L713283 may bind to β-tubulin and favor the formation of αβ-tubulin dimmer. This work provides possible explanation for molecular mechanism of the anticancer agent L713283, and the strategy used here could benefit the investigation of possible target profile for those bioactive agents with unknown mechanisms.