Conformation-Induced Dynamical Heterogeneity of Water in the Solvation Shell of Zwitterionic γ-Aminobutyric Acid.

The structure and dynamics of water molecules around the carboxylate and amino groups of γ-aminobutyric acid (GABA), a primary neurotransmitter in mammals, are investigated by means of ab initio molecular dynamics simulation. Zwitterionic GABA has two major conformations in water, namely, the open and the closed conformations. The angle-averaged one-dimensional structures of water in the solvation shells around the carboxylate and amino groups are found to be quite similar for the closed and open conformations of the solute. The two-dimensional structural correlations, which describe the solvation shell structure with better resolution, reveal some differences in the arrangement of water molecules around the solute for its open and closed conformations. It is found that the dynamics of solvation shells in the two conformations vary only slightly. However, the existence of trapped water between the oppositely charged carboxylate and amino groups of GABA in its closed form is found to give rise to a very different dynamical behavior as compared to the overall solvation shell in the same conformation as well as that in the open conformation. Thus, dynamical heterogeneity at a local level is induced by a change in the conformation of zwitterionic GABA. Such trapped water is not seen in the open form of the solute. A similar type of "connecting water" has also been observed for microsolvated β-alanine in a recent experimental and theoretical study ( Ghassemizadeh J. Phys. Chem. B , 2019 , 123 , 4392 - 4399 ). Thus, the current study shows the variation of binding properties of water with the change in the conformation of zwitterionic GABA, which in turn changes the dynamics of water at a local level. The conformation-induced changes in the water dynamics constitute an example of dynamical heterogeneity of water, which is normally observed in the presence of large biomolecules like proteins, DNA, etc.