Combining the Fragment Molecular Orbital and GRID Approaches for the Prediction of Ligand-Metalloenzyme Binding Affinity: The Case Study of hCA II Inhibitors.

ABSTRACT: Polarization and charge-transfer interactions play an important role in ligand-receptor complexes containing metals, and only quantum mechanics methods can adequately describe their contribution to the binding energy. In this work, we selected a set of benzenesulfonamide ligands of human Carbonic Anhydrase II (hCA II)-an important druggable target containing a Zn²⁺ ion in the active site-as a case study to predict the binding free energy in metalloprotein-ligand complexes and designed specialized computational methods that combine the ab initio fragment molecular orbital (FMO) method and GRID approach. To reproduce the experimental binding free energy in these systems, we adopted a machine-learning approach, here named formula generator (FG), considering different FMO energy ter

SUBMITTER: Paciotti R 

PROVIDER: S-EPMC11313991 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature