title: Isodesmic reaction for accurate theoretical pKa calculations of amino acids and peptides.
abstract: Theoretical and quantitative prediction of pKa values at low computational cost is a current challenge in computational chemistry. We report that the isodesmic reaction scheme provides semi-quantitative predictions (i.e. mean absolute errors of 0.5-1.0 pKa unit) for the pKa1 (α-carboxyl), pKa2 (α-amino) and pKa3 (sidechain groups) of a broad set of amino acids and peptides. This method fills the gaps of thermodynamic cycles for the computational pKa calculation of molecules that are unstable in the gas phase or undergo proton transfer reactions or large conformational changes from solution to the gas phase. We also report the key criteria to choose a reference species to make accurate predictions. This method is computationally inexpensive and makes use of standard density functional theory (DFT) and continuum solvent models. It is also conceptually simple and easy to use for researchers not specialized in theoretical chemistry methods.
authors.affiliation: Department de Química, Universitat de les Illes Balears, Palma de Mallorca 07122, Spain. juan.frau@uib.es.
authors.forename: S
authors.initials: S
authors.lastname: Sastre
authors.affiliation: Institute of Neuroscience and Medicine INM-9, Institute for Advanced Simulations IAS-5. Computational Biomedicine, Forschungszentrum Jülich 52428, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Casasnovas
authors.affiliation: Department de Química, Universitat de les Illes Balears, Palma de Mallorca 07122, Spain. juan.frau@uib.es and Instituto de Investigación Sanitaria de Palma (IdISPa), 07010, Palma, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Muñoz
authors.affiliation: Department de Química, Universitat de les Illes Balears, Palma de Mallorca 07122, Spain. juan.frau@uib.es and Instituto de Investigación Sanitaria de Palma (IdISPa), 07010, Palma, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Frau
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D012997:Solvents