Do electrostatic interactions make a difference in physics-based AutoDock4 scoring function?

Autor: Shaimardanov AR; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation., Shulga DA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation., Palyulin VA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
Jazyk: angličtina
Zdroj: Journal of computational chemistry [J Comput Chem] 2024 Aug 05; Vol. 45 (21), pp. 1806-1820. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1002/jcc.27373
Abstrakt: Physics-based scoring function AutoDock4 is one of the most successfully applied tools in the area of structure-based drug design. However, current scoring functions are still far from being perfect. In a recent work highlighting the strengths and deficiencies of current scoring functions, we discovered that the residual error of ΔG bind predictions made by AutoDock4 is highly correlated to the presence of formally charged fragments in a ligand. In this work, we study how the use of the high-quality atomic charges, applied for contemporary force fields calculation, affects the quality of the experimental ΔG bind prediction by means of AutoDock4. We initially expected that the previously found discrepancy could be attributed to the Gasteiger charges used within AutoDock4. We show that AutoDock4 is, surprisingly, not sensitive to the charges used, and the use of QC-derived atomic charges does not lead to any statistical improvements. We also briefly discuss the role of the explicit empirical hydrogen bond term along with the electrostatic term.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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