Surface hydration and preferential interaction directs the charged amino acids-induced changes in protein stability.

Research paper by Bramhini B Anumalla, N Prakash NP Prabhu

Indexed on: 07 Apr '20Published on: 07 Apr '20Published in: Journal of Molecular Graphics and Modelling


In the present study, we investigate the interaction of amino acid osmolytes, Arg, Lys, Asp and Glu, and a denaturant, guanidinium chloride (Gdm) with proteins. To achieve this, molecular dynamics (MD) simulation of RNase A and α-lactalbumin was performed in the presence of three charged amino acids Arg, Lys, and Asp and the molecular mechanism of amino acid-induced (de)stabilization of the proteins was examined by combining with our earlier report on Glu. As Arg has the side chain similar to that of Gdm and destabilizes the proteins, MD simulation was carried out in the presence of Gdm as well. Radial distribution function and hydration fraction around the protein surface reveals that preferential hydration increases upon the addition of any of the cosolvent; however, the extent of increase is more in the presence of stabilizing cosolvents (stAAs: Lys, Asp and Glu) compared to destabilizing cosolvents (Arg and Gdm). Moreover, the preferential interaction of Arg and Gdm with the proteins is higher than that of stAAs. Residue-level interaction analysis suggests that stAAs preferably interacts with charged amino acids of the proteins whereas Arg and Gdm interactions could be found on almost all the surface exposed residues which might provide higher preferential interaction for these residues. From the results, we propose that the net outcome of preferential hydration versus preferential interaction of the amino acids might determine their effect on the stability of proteins. Copyright © 2020 Elsevier Inc. All rights reserved.