title: The influence of variations of ligand protonation and tautomerism on protein-ligand recognition and binding energy landscape.
abstract: We investigate the influence of variations of ligand protonation and tautomeric states on the protein-ligand binding energy landscape by applying the concept of structural consensus. In docking simulations, allowing full flexibility of the ligand, we explore whether the native binding mode could be successfully recovered using a non-native ligand protonation state. Here, we consider three proteins, dihydrofolate reductase, transketolase, and alpha-trichosanthin, complexed with ligands having multiple tautomeric forms. We find that for the majority of protonation and tautomeric states the native binding mode can be recovered without a great loss of accuracy.
authors.affiliation: De Novo Pharmaceuticals Ltd., Vision Park, Histon, Cambridge CB49ZR, United Kingdom. nikolay.todorov@denovopharma.com
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Todorov
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Monthoux
authors.forename: Ian L
authors.initials: IL
authors.lastname: Alberts
mesh_terms: D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D011506:Proteins / Q000378:metabolism*; D011522:Protons; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D011506:Proteins; D011522:Protons