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Using Atomic Charges to Describe the pKa of Carboxylic Acids

preprint
submitted on 09.08.2020 and posted on 11.08.2020 by Zeynep Pinar Haslak, Sabrina Zareb, Viktorya Aviyente, Gerald Monard
In this study, we present an accurate protocol for the fast prediction of pKa's of carboxylic acids based on the linear relationship between computed atomic charges of the anionic form of the carboxylate fragment and their experimental pKa values. Five charge descriptors, three charge models, three solvent models, gas phase calculations and several DFT methods (combination of eight DFT functionals and fifteen basis sets) were tested. Among those, the best combination to reproduce experimental pKa's is to compute NPA atomic charge using the SMD model at the M06L/6-311G(d,p) level of theory and selecting the maximum atomic charge on carboxylic oxygen atoms (R^2 = 0.955). The applicability of the suggested protocol and its stability along geometrical changes are verified by molecular dynamics simulations performed for a set of aspartate, glutamate and alanine peptides. By reporting the calculated atomic charge of the carboxylate form into the linear relationship derived in this work, it will be possible to estimate accurately the amino acid’s pKa's in protein environment.

History

Email Address of Submitting Author

gerald.monard@univ-lorraine.fr

Institution

Universite de Lorraine

Country

France

ORCID For Submitting Author

0000-0002-3378-3481

Declaration of Conflict of Interest

No conflict of interest

Version Notes

Revision 1.0

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