Issue 16, 2016

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.

Graphical abstract: Isodesmic reaction for accurate theoretical pKa calculations of amino acids and peptides

Supplementary files

Article information

Article type
Paper
Submitted
17 Nov 2015
Accepted
16 Mar 2016
First published
16 Mar 2016

Phys. Chem. Chem. Phys., 2016,18, 11202-11212

Author version available

Isodesmic reaction for accurate theoretical pKa calculations of amino acids and peptides

S. Sastre, R. Casasnovas, F. Muñoz and J. Frau, Phys. Chem. Chem. Phys., 2016, 18, 11202 DOI: 10.1039/C5CP07053H

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