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

ACS Omega
Haresh AjaniMartin Lepšík

Abstract

General and reliable description of structures and energetics in protein-ligand (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 computa...Continue Reading

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Citations

Aug 29, 2019·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Saltuk M EyrilmezPavel Hobza
Jan 10, 2018·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Adam PecinaJindřich Fanfrlík
May 19, 2020·Physical Chemistry Chemical Physics : PCCP·Soohaeng Yoo WillowDavid D L Minh
Jun 3, 2020·Molecular Informatics·Saleh BagheriMohammad Hossein Karimi-Jafari
Jun 14, 2018·Frontiers in Chemistry·Claudio N CavasottoMaria G Aucar
Mar 27, 2020·Journal of Molecular Recognition : JMR·Cemal KöprülüoğluRadim Nencka
Dec 24, 2020·Expert Opinion on Drug Discovery·Julio Caballero
Feb 18, 2020·Journal of Chemical Information and Modeling·Kristian Kříž, Jan Řezáč

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Methods Mentioned

BETA
X-ray

Software Mentioned

PBDbind
AutoDock
AMBER
AutoDock Vina
Surflex Dock
UCSF Dock
Glide SP
AMBER14
Schrödinger
Autodock4

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