Acta Phys. -Chim. Sin. ›› 2013, Vol. 29 ›› Issue (02): 423-430.doi: 10.3866/PKU.WHXB201211212

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Molecular Dynamics Simulations of Interactional Mechanism and Binding Energy Calculations between Kinase ABL and Small Molecules Binding at Myristoyl Pocket

YANG Li-Jun1, LIU Qian1, YUAN Wen-Bin1, YANG Sheng-Yong2   

  1. 1 Chemistry Synthesis and Pollution Key Laboratory of Sichuan Province, College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637009, Sichuan Province, P. R. China;
    2 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, P. R. China
  • Received:2012-09-18 Revised:2012-11-21 Published:2013-01-14
  • Supported by:

    The project was supported by the Scientific Research Fund of Sichuan Provincial Education Department, China (11ZA294) and Scientific Research Starting Foundation of ChinaWest Normal University, China (10B006).


We performed molecular dynamics simulations on complexes of ABL to investigate the binding of imatinib, P16 (binding at the ATP pocket), and STJ, MS7, MS9, 3YY, and MYR (binding at the myristoyl pocket). The calculated binding energies were then decomposed to determine the ligand-residue pair interactions, using the generalized Born surface area (GBSA) method. The results showed that the binding energies are almost the same for STJ, MS7, and MS9, and their absolute values are larger than those of 3YY and MYR. The decomposition of the binding energy revealed that three residues (ILE502, VAL506, and LEU510) contribute significantly to hold the αI-helix in a bent conformation in the STJ-ABL and MYR-ABL complexes. The root mean square deviation (RMSD) values for the residues forming myristoyl pocket showed that the inhibitors in this pocket decrease the flexibility of the corresponding residues.

Key words: Molecular dynamics, Kinase, Myristoyl pocket, Free energy, Inhibitor