title: Who cares for the protons?
abstract: It is tempting to use standard protonation states for the analysis of protein-ligand interactions. Two different pK(a) calculation methods, PROPKA (protein pK(a)) and MCCE (multi conformation continuum electrostatics), were applied to challenge this convenient behavior. As data basis, we selected five recently approved drugs for which structural information of the protein-drug complex is available. We analyzed the pK(a) calculations in terms of a measure termed BIPS (binary protonation states) recently introduced by us. Both methods agree in detecting the majority of the sites with atypical BIPS values. However, when using only one method, some of the atypcial BIPS value would have been missed. Therefore, we recommend using both methods to set such an interpretation on a solid basis.
authors.affiliation: Merck KGaA, Computational Chemistry, Frankfurter Strasse 250, D-64293 Darmstadt, Germany. paul.czodrowski@merckgroup.com
authors.forename: Paul
authors.initials: P
authors.lastname: Czodrowski
mesh_terms: D006863:Hydrogen-Ion Concentration; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011522:Protons
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins; D011522:Protons