Molecular Interaction of Human Brain Acetylcholinesterase with a Natural Inhibitor Huperzine-B: An Enzoinformatics Approach

Title:Molecular Interaction of Human Brain Acetylcholinesterase with a Natural Inhibitor Huperzine-B: An Enzoinformatics Approach

Volume: 13 Issue: 3

Author(s): Aftab Alam, Sibhghatulla Shaikh, Syed S. Ahmad, Mohammad A. Ansari, Shahnawaz Shakil, Syed M.D. Rizvi, Shazi Shakil, Mohammad Imran, Mohammad Haneef, Adel M. Abuzenadah and Mohammad A. Kamal

Affiliation:

Keywords: Acetylcholinesterase, autodock4.2, hydrophobic interactions, catalytic site.

Abstract: The present study emphasizes the molecular interactions between human brain acetylcholinesterase (AChE) and the natural ligand Huperzine-B and its comparison to ‘AChE-Tolserine interactions’. Docking between Huperzine-B and AChE was performed using ‘Autodock4.2’. Hydrophobic interactions and hydrogen bonds both play an equally important role in the correct positioning of Huperzine-B within the ‘catalytic site’ of AChE to permit docking. However, docking of Tolserine to AChE is largely dominated by hydrophobic interactions. Such information may aid in the design of versatile AChE-inhibitors, and is expected to aid in safe clinical use of Huperzine-B. Scope still remains in the determination of the three-dimensional structure of AChE-Huperzine-B complex by X-ray crystallography to validate the described data. Furthermore, this study confirms that Huperzine-B is a more efficient inhibitor of human brain AChE compared to tolserine with reference to K_i and ΔG values.

Cite this article as:

Alam Aftab, Shaikh Sibhghatulla, Ahmad S. Syed, Ansari A. Mohammad, Shakil Shahnawaz, Rizvi M.D. Syed, Shakil Shazi, Imran Mohammad, Haneef Mohammad, Abuzenadah M. Adel and Kamal A. Mohammad, Molecular Interaction of Human Brain Acetylcholinesterase with a Natural Inhibitor Huperzine-B: An Enzoinformatics Approach, CNS & Neurological Disorders - Drug Targets 2014; 13 (3) . https://dx.doi.org/10.2174/18715273113126660163