Superior Performance of the SQM/COSMO Scoring Functions in Native Pose Recognition of Diverse Protein-Ligand Complexes in Cognate Docking

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00487122" target="_blank" >RIV/61388963:_____/17:00487122 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/17:73584360

Výsledek na webu

<a href="https://pubs.acs.org/doi/full/10.1021/acsomega.7b00503" target="_blank" >https://pubs.acs.org/doi/full/10.1021/acsomega.7b00503</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsomega.7b00503" target="_blank" >10.1021/acsomega.7b00503</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Superior Performance of the SQM/COSMO Scoring Functions in Native Pose Recognition of Diverse Protein-Ligand Complexes in Cognate Docking

Popis výsledku v původním jazyce

General and reliable description of structures and energetics in proteinligand (PL) binding using the docking/scoring methodology has until now been elusive. We address this urgent deficiency of scoring functions (SFs) by the systematic development of corrected semiempirical quantum mechanical (SQM) methods, which correctly describe all types of noncovalent interactions and are fast enough to treat systems of thousands of atoms. Two most accurate SQM methods, PM6-D3H4X and SCC-DFTB3-D3H4X, are coupled with the conductor-like screening model (COSMO) implicit solvation model in so-called ”SQM/COSMO” SFs and have shown unique recognition of native ligand poses in cognate docking in four challenging PL systems, including metalloprotein. Here, we apply the two SQM/COSMO SFs to 17 diverse PL complexes and compare their performance with four widely used classical SFs (Glide XP, AutoDock4, AutoDock Vina, and UCSF Dock). We observe superior performance of the SQM/COSMO SFs and identify challenging systems. This method, due to its generality, comparability across the chemical space, and lack of need for any system-specific parameters, gives promise of becoming, after comprehensive large-scale testing in the near future, a useful computational tool in structure-based drug design and serving as a reference method for the development of other SFs.

Název v anglickém jazyce

Superior Performance of the SQM/COSMO Scoring Functions in Native Pose Recognition of Diverse Protein-Ligand Complexes in Cognate Docking

Popis výsledku anglicky

General and reliable description of structures and energetics in proteinligand (PL) binding using the docking/scoring methodology has until now been elusive. We address this urgent deficiency of scoring functions (SFs) by the systematic development of corrected semiempirical quantum mechanical (SQM) methods, which correctly describe all types of noncovalent interactions and are fast enough to treat systems of thousands of atoms. Two most accurate SQM methods, PM6-D3H4X and SCC-DFTB3-D3H4X, are coupled with the conductor-like screening model (COSMO) implicit solvation model in so-called ”SQM/COSMO” SFs and have shown unique recognition of native ligand poses in cognate docking in four challenging PL systems, including metalloprotein. Here, we apply the two SQM/COSMO SFs to 17 diverse PL complexes and compare their performance with four widely used classical SFs (Glide XP, AutoDock4, AutoDock Vina, and UCSF Dock). We observe superior performance of the SQM/COSMO SFs and identify challenging systems. This method, due to its generality, comparability across the chemical space, and lack of need for any system-specific parameters, gives promise of becoming, after comprehensive large-scale testing in the near future, a useful computational tool in structure-based drug design and serving as a reference method for the development of other SFs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

ACS Omega

ISSN

2470-1343

e-ISSN

—

Svazek periodika

2

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

4022-4029

Kód UT WoS článku

000409909900101

EID výsledku v databázi Scopus

2-s2.0-85028929358