Evaluations of the conformational search accuracy of CAMDAS using experimental three-dimensional structures of protein-ligand complexes

24th IUPAP Conference on Computational Physics

物理学;计算机科学

Oda, A.^1,2,3 ; Yamaotsu, N.^4 ; Hirono, S.^4 ; Takano, Y.^3 ; Fukuyoshi, S.^1 ; Nakagaki, R.^1 ; Takahashi, O.^2

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan^1

Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan^2

Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan^3

School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan^4

关键词: Conformational search;    High temperature;    Md calculations;    MD simulation;    Protein-ligand complexes;    Root mean square deviations;    Small molecules;    Three-dimensional structure;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/454/1/012028/pdf
DOI  :  10.1088/1742-6596/454/1/012028

学科分类：计算机科学（综合）

来源: IOP

【 摘 要 】

CAMDAS is a conformational search program, through which high temperature molecular dynamics (MD) calculations are carried out. In this study, the conformational search ability of CAMDAS was evaluated using structurally known 281 protein-ligand complexes as a test set. For the test, the influences of initial settings and initial conformations on search results were validated. By using the CAMDAS program, reasonable conformations whose root mean square deviations (RMSDs) in comparison with crystal structures were less than 2.0 A could be obtained from 96% of the test set even though the worst initial settings were used. The success rate was comparable to those of OMEGA, and the errors of CAMDAS were less than those of OMEGA. Based on the results obtained using CAMDAS, the worst RMSD was around 2.5 A, although the worst value obtained was around 4.0 A using OMEGA. The results indicated that CAMDAS is a robust and versatile conformational search method and that it can be used for a wide variety of small molecules. In addition, the accuracy of a conformational search in relation to this study was improved by longer MD calculations and multiple MD simulations.