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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.

SUBMITTER: Jameel F

PROVIDER: S-EPMC11305096 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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

Jameel Froze F Stein Matthias M

Physical chemistry chemical physics : PCCP 20240807 31

Calculating the Gibbs energies of binding of ligand-receptor systems with a thermochemical accuracy of ± 1 kcal mol<sup>-1</sup> 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 <i>meta</i>-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 o ...[more]

PMID: 39073067

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