Towards good correlation between fragment molecular orbital interaction energies and experimental IC₅₀ for ligand binding: A case study of p38 MAP kinase.

ABSTRACT: We describe several procedures for the preprocessing of fragment molecular orbital (FMO) calculations on p38 mitogen-activated protein (MAP) kinase and discuss the influence of the procedures on the protein-ligand interaction energies represented by inter-fragment interaction energies (IFIEs). The correlation between the summation of IFIEs for a ligand and amino acid residues of protein (IFIE-sum) and experimental affinity values (IC₅₀) was poor when considered for the whole set of protein-ligand complexes. To improve the correlation for prediction of ligand binding affinity, we carefully classified data set by the ligand charge, the DFG-loop state (DFG-in/out loop), which is characteristic of kinase, and the scaffold of ligand. The correlation between IFIE-sums and the activity

SUBMITTER: Sheng Y 

PROVIDER: S-EPMC6226568 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature