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

Abstract

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.

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“…The LigPrep module in the Maestro Schrödinger suite was used to set up and start the ligand preparation step. LigPrep uses sophisticated rules to convert structure from 2D to 3D by adding hydrogens and considering bond lengths or angles based on the correct chiralities, tautomers, and ring conformations in the ligands which helps to reduce downstream computational errors [ 37 ]. The possible protonation states were set at a physiological pH range of 7 ± 2 with the help of the Epik ionization program [ 38 ], and the OPLS4 force field was used for energy minimization [ 39 , 40 ].…”

“…Polar hydrogen atoms were added, water molecules beyond 5 Å from het groups were removed, charges were defined at default pH (7 ± 2) using Epik [ 38 ], and bond orders were assigned. Finally, restrained minimization was carried out using an OPLS4 force field to alleviate steric clashes while heavy atoms converged at a predefined RMSD value of 0.30 Å [ 37 , 44 ].…”

Computational Target-Based Screening of Anti-MRSA Natural Products Reveals Potential Multitarget Mechanisms of Action through Peptidoglycan Synthesis Proteins

“…LigPrep uses a set of rules to correct chiralities, tautomers, and ring conformations in ligands, reducing downstream computational errors. 23 The OPLS3e force field was selected for energy minimization of the ligands because it has the benefit of accurately predicting protein–ligand binding affinities based on past performance. 24 The protonation states were set to a physiological pH range of 7 ± 2 using the Epik ionization program.…”

Molecular Docking and ADME Analysis of L-Phe -L-Tyr Dipeptide

“…The aim of molecular docking is to provide the prediction of a ligand and receptor complex [14]. To understand the reported antihypertensive activity of Phe-Tyr dipeptide, molecular docking studies were carried out using specific target receptor (ACE and AT1R).…”