Nonbonded Force Field Parameters from Minimal Basis Iterative Stockholder Partitioning of the Molecular Electron Density Improve CB7 Host–Guest Affinity Predictions

• DOI: 10.1021/acs.jcim.2c00316
• Publication Date: 2022-08-12T07:14:04Z
• Authors: Duván González; Luis Macaya; Carlos Castillo-O...; Toon Verstraelen; Stefan Vogt-Geisse; Esteban Vöhringer...
• Keywords: Force Field; Adamantane; London dispersion force; Hamiltonian (control theory)

Binding affinity prediction by means of computer simulation has been increasingly incorporated in drug discovery projects. Its wide application, however, is limited the accuracy free energy calculations. The main error sources are force fields used to describe molecular interactions and incomplete sampling configurational space. Organic host–guest systems have address field quality because they share similar found ligands receptors, their rigidity facilitates sampling. Here, we test binding for 14 guests with an aromatic or adamantane core CB7 host using electron density derived nonbonded parameters. We developed a computational workflow written Python derive atomic charges Lennard-Jones parameters Minimal Basis Iterative Stockholder method polarized several configurations each guest bound unbound states. resulting improve prediction, especially which repulsive exchange dispersion dominate.