Assessing the performance of docking scoring function, FEP, MM-GBSA, and QM/MM-GBSA approaches on a series of PLK1 inhibitors

Chunlan Pu; Guoyi Yan; Jianyou Shi; Rui Li

doi:10.1039/c7md00184c

Assessing the performance of docking scoring function, FEP, MM-GBSA, and QM/MM-GBSA approaches on a series of PLK1 inhibitors

Medchemcomm. 2017 May 22;8(7):1452-1458. doi: 10.1039/c7md00184c. eCollection 2017 Jul 1.

Authors

Chunlan Pu¹, Guoyi Yan¹, Jianyou Shi², Rui Li¹

Affiliations

¹ Cancer Center , West China Hospital , Sichuan University, and Collaborative Innovation Center for Biotherapy , 610041 Sichuan , P. R. China . Email: lirui@scu.edu.cn ; ; Tel: +86 28 85164063.
² Individualized Medication Key Laboratory of Sichuan Province , Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital , Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital , School of Medicine , Center for Information in Medicine , University of Electronic Science and Technology of China , Chengdu , 610072 Sichuan , P. R. China . Email: shijianyoude@126.com.

Abstract

Over-expressed polo-like kinases 1, a key regulator of cell mitosis, is associated with carcinogenesis and poor prognosis. It is very necessary to develop a reliable computational affinity prediction protocol targeting PLK1. In this study, the performance of different docking scoring function, free energy perturbation, MM-GBSA and QM/MM-GBSA were evaluated. The ranking capability of FEP is the best with r_s = 0.854. However, the r_s obtained from MM-GBSA can reach 0.767, which requires only about one-eighth of the simulation time of FEP. As for the sampling method, single long molecular dynamics (SLMD) surpass the multiple short molecular dynamics (MSMD) in ranking of the 20 congeneric compounds by about 0.1 in r_s. In addition, ligands treated by QM can significantly improve the ranking performance. As for the docking scoring functions, a force field-based scoring function is more suitable for ranking congeneric compounds.