Molecular Docking and Molecular Dynamics Studies of L-Glycyl-L-Glutamic Acid Dipeptide

The Gly-Glu (GE) dipeptide, which acts as a neurotransmitter, is made of glycine and glutamic amino acids that are used in the treatment of neurological diseases such as Schizophrenia, Parkinson and Alzheimer. Gly-Glu dipeptide is an important peptide structure that helps prevent neuronal degeneration, especially in Alzeimer's disease. Caspases which are cysteine proteases play a crucial role for apoptotic death of neurons in Alzheimer’s disease. In patients with Alzheimer's disease, there was an increase in caspase-3 immunoreactivity in the death of pyramidal neurons, where the initial sites of neuronal loss were proven (Gervais et al. 1999). The molecular structure of the GE dipeptide having anti-apoptotic properties is very important for clarifying the activation mechanism with caspase-3 protein. Molecular dynamics and molecular docking calculations were applied to elucidate the most stable molecular conformation and to grasp the mechanism of activity of GE with caspase-3. Firstly, GROMACS program was used to reveal the conformation variations of the GE within the body. The stability of the peptide is ensured by confinement in 704 water molecules. Secondly, Glide SP (standard precision) module of the Maestro 11.4 version in the Schrodinger Software program was used to determine the linkages and activity of the peptide with the caspase-3 protein. In this study, the structure of this dipeptide, pharmacological properties and its mechanism of action with caspase-3 protein were investigated for the first time by molecular dynamics and docking calculations.