title: 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.
authors.affiliation: European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Beshnova
authors.affiliation: European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Pereira
authors.affiliation: European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Lamzin
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D055808:Drug Discovery; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries
keywords: ARP/wARP; LigEnergy; automated identification of crystallographic ligands; protein–ligand interaction energy; protein–ligand interactions; structure validation