Understanding the Structure-Activity Relationship through Density Functional Theory: A Simple Method Predicts Relative Binding Free Energies of Metalloenzyme Fragment-like Inhibitors.

ABSTRACT: Despite being involved in several human diseases, metalloenzymes are targeted by a small percentage of FDA-approved drugs. Development of novel and efficient inhibitors is required, as the chemical space of metal binding groups (MBGs) is currently limited to four main classes. The use of computational chemistry methods in drug discovery has gained momentum thanks to accurate estimates of binding modes and binding free energies of ligands to receptors. However, exact predictions of binding free energies in metalloenzymes are challenging due to the occurrence of nonclassical phenomena and interactions that common force field-based methods are unable to correctly describe. In this regard, we applied density functional theory (DFT) to predict the binding free energies and to understand the str

SUBMITTER: Vasile S 

PROVIDER: S-EPMC10285960 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature