Impressive Enrichment of Semiempirical Quantum Mechanics-Based Scoring Function: HSP90 Protein with 4541 Inhibitors and Decoys

0509455 - ÚOCHB 2020 RIV DE eng J - Článek v odborném periodiku
Eyrilmez, Saltuk M. - Köprülüoglu, Cemal - Řezáč, Jan - Hobza, Pavel
Impressive Enrichment of Semiempirical Quantum Mechanics-Based Scoring Function: HSP90 Protein with 4541 Inhibitors and Decoys.
ChemPhysChem. Roč. 20, č. 21 (2019), s. 2759-2766. ISSN 1439-4235. E-ISSN 1439-7641
Grant CEP: GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963
Klíčová slova: docking * enrichment * non-covalent interactions * semiempirical quantum mechanics-based scoring function * virtual screening
Obor OECD: Physical chemistry
Impakt faktor: 3.144, rok: 2019
Způsob publikování: Omezený přístup
https://onlinelibrary.wiley.com/doi/abs/10.1002/cphc.201900628

This paper describes the excellent performance of a newly developed scoring function (SF), based on the semiempirical QM (SQM) PM6‐D3H4X method combined with the conductor‐like screening implicit solvent model (COSMO). The SQM/COSMO, Amber/GB and nine widely used SFs have been evaluated in terms of ranking power on the HSP90 protein with 72 biologically active compounds and 4469 structurally similar decoys. Among conventional SFs, the highest early and overall enrichment measured by EF1 and AUC% obtained using single‐scoring‐function ranking has been found for Glide SP and Gold‐ASP SFs, respectively (7, 75 % and 3, 76 %). The performance of other standard SFs has not been satisfactory, mostly even decreasing below random values. The SQM/COSMO SF, where P−L structures were optimised at the advanced Amber level, has resulted in a dramatic enrichment increase (47, 98 %), almost reaching the best possible receiver operator characteristic (ROC) curve. The best SQM frame thus inserts about seven times more active compounds into the selected dataset than the best standard SF.
Trvalý link: http://hdl.handle.net/11104/0300194