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

Year 2019, Volume: 3 Issue: 1, 1 - 9, 30.03.2019

Bilge Bıçak , Serda Kecel Gündüz , Yağmur Kökcü Ayşen E. Özel Sevim Akyüz

https://doi.org/10.30516/bilgesci.476841

Cited By: 14

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.

Keywords

Gly-Glu, dipeptide, Molecular Dynamics, Molecular Docking, ADME

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