Structure-Based Design and Molecular Dynamics Simulations of Pentapeptide AEYTR as a Potential Acetylcholinesterase Inhibitor

Vivitri Dewi Prasasty; Enade Perdana Istyastono

doi:10.22146/ijc.46329

Structure-Based Design and Molecular Dynamics Simulations of Pentapeptide AEYTR as a Potential Acetylcholinesterase Inhibitor

https://doi.org/10.22146/ijc.46329

Vivitri Dewi Prasasty⁽¹⁾, Enade Perdana Istyastono^(2*)

(1) Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia
(2) Faculty of Pharmacy, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282
(*) Corresponding Author

Abstract

Structure-based virtual screening protocol to identify potent acetylcholinesterase inhibitors was retrospectively validated. The protocol could be employed to examine the potential of designed compounds as novel acetylcholinesterase inhibitors. In a research project designing short peptides as acetylcholinesterase inhibitors, peptide AEYTR emerged as one of the potential inhibitors. This article presents the design of AEYTR assisted by the validated protocol and guided by literature reviews followed by molecular dynamics studies to examine the interactions of the pentapeptide in the binding pocket of the acetylcholinesterase enzyme. The molecular dynamics simulations were performed using YASARA Structure in Google Cloud Platform. The peptide AEYTR was identified in silico as a potent acetylcholinesterase inhibitor with the average free energy of binding (DG) of -19.138 kcal/mol.

Keywords

Acetylcholinesterase; Pentapeptide; Molecular Dynamics; YASARA Structure; Google Cloud Platform

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DOI: https://doi.org/10.22146/ijc.46329