A systematic analysis of intermolecular interactions of cytochrome P450s with their ligands

Abstract

Statistical analysis of 6,859 intermolecular contacts in experimentally determined spatial structures of cytochromes P450 (CYPs) with ligands, stored in the Protein Data Bank (PDB), was performed. The most frequent types of contacts are hydrophobic interactions, hydrogen bonds, water bridges, and π-stacking interactions. Domain-specific analysis of the interaction types allowed identifying of interaction patterns, which are specific for bacterial and eukaryotic proteins. Among these patterns amino acids (AA) involved in ligand binding are preferred. The high fraction of hydrophobic contacts reflects the fact that many of the tested ligands are lead compounds and that the active site of most CYPs is more hydrophobic than hydrophilic. The results highlight cytochromes P450 specific ligand-binding peculiarities, which are of great importance for molecular structure embedding in deep learning neural networks and for the development of efficient scoring functions to analyze molecular docking results.