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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00509455" target="_blank" >RIV/61388963:_____/19:00509455 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/19:73596354

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/cphc.201900628" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/cphc.201900628</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cphc.201900628" target="_blank" >10.1002/cphc.201900628</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ChemPhysChem

ISSN

1439-4235

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

2759-2766

Kód UT WoS článku

000486210800001

EID výsledku v databázi Scopus

2-s2.0-85073948335