Molecular dynamics simulations of aqueous glutamate and the gly-pro-glu (GPE) tripeptide

Abstract

Biomolecular systems, in particular those involving proteins and their constituents, have been the focus of much research in the last century. The relationship between experiment, development of models and simulation has enabled vast improvements in our knowledge of subjects such as protein folding and the processes by which key biomolecules affect the human body. In particular, vital information can be obtained from understanding the building blocks of polypeptides and proteins involved in these processes. This work focuses on simulating two such building blocks; glutamate, the salt of the proteinogenic amino acid, glutamic acid, and glycine-proline-glutamate, or GPE, a related tripeptide. Both are important in neurotransmission processes in the brain. Glutamate is the most abundant neurotransmitter in the central nervous system and GPE is an important neuroprotective agent. This work aims to elucidate the key structural properties of aqueous solutions of glutamate and GPE, focusing on the solute-solute as well as the solute-solvent interactions. Both systems were considered with classical empirical potentials using the CHARMM22 force-fi eld. The glutamate system has also been studied using Car-Parrinello Molecular Dynamics and classical parallel tempering. In both the aqueous glutamate and GPE systems the molecules formed a large proportion of bifurcated bonding motifs with both carboxyl groups, but not with the amin (N-terminal) of the molecules. Bifurcated bonds form between solute molecules as well as in the solute-solvent interactions. The structure of the glutamate solution was found to be dependent on the initial con figuration and thus the parallel tempering simulations enabled better sampling of the conformational landscape. In addition, in the glutamate system single water molecules form a stable structure by bonding to both the amine (N-terminal) and C -carboxyl within the same glutamate molecule.