Statistical Estimation of the Protein-Ligand Binding Free Energy Based On Direct Protein-Ligand Interaction Obtained by Molecular Dynamics Simulation

Pharmaceuticals

Yoshifumi Fukunishi¹ 

[1] Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-3-26, Aomi, Koto-ku, Tokyo 135-0064, Japan

关键词: protein-ligand docking;    molecular dynamics simulation;    protein-ligand binding free energy;   

DOI  :  10.3390/ph5101064

来源: mdpi

【 摘 要 】

We have developed a method for estimating protein-ligand binding free energy (ΔG) based on the direct protein-ligand interaction obtained by a molecular dynamics simulation. Using this method, we estimated the ΔG value statistically by the average values of the van der Waals and electrostatic interactions between each amino acid of the target protein and the ligand molecule. In addition, we introduced fluctuations in the accessible surface area (ASA) and dihedral angles of the protein-ligand complex system as the entropy terms of the ΔG estimation. The present method included the fluctuation term of structural change of the protein and the effective dielectric constant. We applied this method to 34 protein-ligand complex structures. As a result, the correlation coefficient between the experimental and calculated ΔG values was 0.81, and the average error of ΔG was 1.2 kcal/mol with the use of the fixed parameters. These results were obtained from a 2 nsec molecular dynamics simulation.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.