Knowledge-Based Scoring Functions in Drug Design. 1. Developing a Target-Specific Method for Kinase-Ligand Interactions
Protein kinases are attractive targets for therapeutic interventions in many diseases. Due to their importance in drug discovery, a kinase familyspecific potential of mean force (PMF) scoring function, kinase-PMF, was developed to assess the binding of ATP-competitive kinase inhibitors. It is hypothesized that target-specific PMF scoring functions may achieve increased performance in scoring along with the growth of the PDB database. The kinase-PMF inherits the functions and atom types in PMF04 and uses a kinase data set of 872 complexes to derive the potentials. The performance of kinasePMF was evaluated with an external test set containing 128 kinase crystal structures. We compared it with eight scoring functions commonly used in computer-aided drug design, either in terms of the retrieval rate of retrieving right conformations or a virtual screening study. The evaluation results clearly demonstrate that a target-specific scoring function is a promising way to improve prediction power in structure-based drug design compared With other general scoring functions. To provide this rescoring service for researchers, a publicly accessible Web site was established at http://202.127.30.184:8080/scoring/index.jsp.
Mengzhu Xue Mingyue Zheng Bing Xiong Yanlian Li Hualiang Jiang Jingkang Shen
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, China 201203
国际会议
武汉
英文
280-288
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）