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

21 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Calculating the Gibbs energies of binding of ligand-receptor systems with a thermochemical accuracy of ± 1 kcal/mol is challenge to computational approaches. A semi-empirical quantum chemical exploration of the conformational space of host, ligand and complexes followed by a multi-level refinement of poses 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 receptor with such an accuracy. The accurate treatment of a small number of poses outperforms system-specific force-matching and alchemical transfer model approaches without an extensive sampling and intergration.


Gibbs energies binding

Supplementary materials

Supplementary Information
Full computational details and calculated ligand-receptor Gibbs energies of binding for SAMPL8 and SAMPL9 challenges at all levels of theory.

Supplementary weblinks


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