Issue 31, 2024

Chemical accuracy for ligand-receptor binding Gibbs energies through multi-level SQM/QM calculations

Abstract

Calculating the Gibbs energies of binding of ligand-receptor systems with a thermochemical accuracy of ± 1 kcal mol−1 is a challenge to computational approaches. After exploration of the conformational space of the host, ligand and their resulting complexes upon coordination by semi-empirical GFN2 MD and meta-MD simulations, the systematic refinement through a multi-level improvement of binding modes in terms of electronic energies and solvation is able to give Gibbs energies of binding of drug molecules to CB[8] and β-CD macrocyclic receptors with such an accuracy. The accurate treatment of a small number of structures outperforms system-specific force-matching and alchemical transfer model approaches without an extensive sampling and integration.

Graphical abstract: Chemical accuracy for ligand-receptor binding Gibbs energies through multi-level SQM/QM calculations

Supplementary files

Article information

Article type
Paper
Submitted
14 Apr 2024
Accepted
18 Jul 2024
First published
19 Jul 2024
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2024,26, 21197-21203

Chemical accuracy for ligand-receptor binding Gibbs energies through multi-level SQM/QM calculations

F. Jameel and M. Stein, Phys. Chem. Chem. Phys., 2024, 26, 21197 DOI: 10.1039/D4CP01529K

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