Estimation of the protein-ligand interaction energy for model building and validation.

ABSTRACT: Macromolecular X-ray crystallography is one of the main experimental techniques to visualize protein-ligand interactions. The high complexity of the ligand universe, however, has delayed the development of efficient methods for the automated identification, fitting and validation of ligands in their electron-density clusters. The identification and fitting are primarily based on the density itself and do not take into account the protein environment, which is a step that is only taken during the validation of the proposed binding mode. Here, a new approach, based on the estimation of the major energetic terms of protein-ligand interaction, is introduced for the automated identification of crystallographic ligands in the indicated binding site with ARP/wARP. The applicability of the method to the validation of protein-ligand models from the Protein Data Bank is demonstrated by the detection of models that are `questionable' and the pinpointing of unfavourable interatomic contacts.

SUBMITTER: Beshnova DA 

PROVIDER: S-EPMC5349431 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature