Abstract

This study revolves around therapeutic importance of natural alkaloids known as beta carbolines. Beta carboline belongs to a group of indole alkaloids and consist of pyridine ring that is fused to an indole skeleton. These alkaloids serve as the most promising candidates for the inhibition of acetylcholinesterase and can be used in the treatment of Alzheimer’s disease. A detailed computational analysis of beta carboline alkaloids with acetylcholinesterase has been carried out using Molecular Docking method.

To accomplish the task, a ligand dataset of simple derivatives of beta carboline is constructed that includes Huperzine A, Galantamine, norharmane, Tryptoline, Pinoline, Harmane, Harmine and Harmaline. The 3D structure of acetylcholinesterase has been used as a receptor. The identification of binding site is a crucial step in validation of computational docking results. So, the crystal structure of acetylcholinesterase complexed with huperzine A (PDB ID: 4EY5) was retrieved from Protein Data Bank (PDB) as a reference to identify the binding residues. As huperzine A is an alkaloid possessing acetylcholine inhibition properties, its interaction with selected acetylcholinesterase residues could serve as binding pocket of the receptor. So, the binding site residues of this complex were analyzed using 2D interaction diagram via Ligplot. The residues involved in the interaction of crystallized structure of acetylcholinesterase with huperzine are Tyr133, Tyr119, Gly120, Gly126, Gly122, Ser125, Tyr337, Gly121, Tyr124, His447, Trp86, Ser203, Glu202. To verify the interacting residues, acetylcholinesterase was detached from huperzine A and again redocked.