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Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations: The Isoelectric Points of Amino Acids as a Case Study
journal contribution
posted on 2020-03-10, 15:03 authored by Jacinto Sandoval-Lira, Gustavo Mondragón-Solórzano, Leonardo I. Lugo-Fuentes, Joaquín Barroso-FloresTheoretical calculation of equilibrium
dissociation constants is a very computationally demanding and time-consuming
process since it requires an extremely accurate computation of the
solvation free energy changes for each of the species involved. By
correlating the minimum surface electrostatic potential (VS,min) on the nitrogen atom of several aliphatic amino
groupscalculated at the density functional theory (DFT) ωB97X-D/cc-pVDZ
level of theorywe obtained regression models for each kind
of substitution pattern from which we interpolate their corresponding
pKb values with remarkable accuracy: primary R2 = 0.9519; secondary R2 = 0.9112; and tertiary R2 = 0.8172
(N = 20 for each family). These models were validated
with tests sets (N = 5) with mean absolute error
(MAE) values of 0.1213 (primary), 0.4407 (secondary), and 0.3057 (tertiary).
Combining this ansatz with another previously reported by our group
to estimate pKa values [Caballero-García,
G.; et al. Molecules 2019, 24(1), 79] we are able
to reproduce the isoelectric points of 13 amino acids with no titrable
side chains with MAE = 0.4636 pI units.