Where does charge reside in amino acids? The effect of side-chain protonation state on the atomic charges of Asp, Glu, Lys, His and Arg

Quantum topological atomic charges have been calculated at B3LYP/apc-1 level to identify where the charge is located on amino acid residues when the side-chain has been either protonated (Arg, Lys, His) or deprotonated (Glu, Asp). All energy local energy minima in the Ramachandran map of each (neutral) amino acid were populated with a number of distorted molecular geometries, summing up to a thousand geometries for each amino acid. The majority of the molecular charge is found on the side-chain (81–100%), with a large percentage of the charge located on the functional group undergoing protonation/deprotonation. Each side-chain (or residue) methylene group was found to act as an insulator between an amino acid’s backbone and its side-chain because it accepts the majority of charge not located on the side-chain. As a result there is no significant charge on backbone atoms relative to the neutral molecule. In the case of His+ and Arg+, where the charge is spread over a large number of atoms due to resonance, the influence of the positive charge on the backbone atoms is reduced.