Charge Regulation of Natural Amino Acids in Aqueous Solutions

The aim of this work is to develop a predictive model to describe the electrostatic behavior of 20 natural amino acids under diverse solution conditions. A coarse-grained model is proposed to account for the key ingredients of thermodynamic nonideality arising from the interaction of amino acids with various solvated ions in an aqueous solution including the molecular volume excluded effects, solvent-mediated electrostatic interactions, van der Waals attraction, and hydrophobic and hydration forces. With a small set of parameters characterizing the intermolecular interactions and dissociation equilibrium, the thermodynamic model is able to correlate extensive experimental data for the activity coefficients and solubility of amino acids in pure water and in aqueous sodium chloride solutions. Moreover, it predicts apparent equilibrium constants for the charge regulation of all amino acids in excellent agreement with experimental data. Importantly, the thermodynamic model allows for the extrapolation of the intrinsic equilibrium constants for amino-acids conversion among different charge states (viz., negative, neutral, and positive charges) thereby enabling the prediction of the charge behavior for all natural amino acids under arbitrary solution conditions.