A molecular interaction field describing nonconventional intermolecular interactions and its application to protein–ligand interaction prediction

In this study, we developed a novel MIF calculation method that describes nonconventional interactions. This method evaluates the MIF as the interaction energy between the target ligand molecule and probe molecule. To describe the nonconventional interactions, our method employs quantum chemical calculations with four types of probe molecules. The calculated MIFs for casein kinase 2 (CK2) inhibitors correctly identify the halogen bond, CH/π, and CH/O interactions formed in the CK2/inhibitor complexes. Additionally, we have developed a method for calculating the protein–ligand interaction energy (Eint) based on the MIF and a coarse-grained protein model. The calculated interaction energies for CK2 inhibitors correlate with the experimental log(Ki) values. Thus, MIF and Eint obtained by our method show promise as descriptors for protein-ligand interaction prediction by considering nonconventional noncovalent interactions.Graphical abstract
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research