An Assessment of Dispersion-Corrected DFT Methods for Modeling Nonbonded Interactions in Protein Kinase Inhibitor Complexes.

ABSTRACT: Accurate modeling of nonbonded interactions between protein kinases and their small molecule inhibitors is essential for structure-based drug design. Quantum chemical methods such as density functional theory (DFT) hold significant promise for quantifying the strengths of these key protein-ligand interactions. However, the accuracy of DFT methods can vary substantially depending on the choice of exchange-correlation functionals and associated basis sets. In this study, a comprehensive benchmarking of nine widely used DFT methods was carried out to identify an optimal approach for quantitative modeling of nonbonded interactions, balancing both accuracy and computational efficiency. From a database of 2139 kinase-inhibitor crystal structures, a diverse library of 49 nonbonded interaction mot

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC11154270 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature