Volume 4 Supplement 1

7th German Conference on Chemoinformatics: 25 CIC-Workshop

Open Access

Identification of hot-spot regions of N-type Ca2+ channel receptor by homology modeling and molecular dynamics study, for structure-based blocker design

Journal of Cheminformatics20124(Suppl 1):P30

DOI: 10.1186/1758-2946-4-S1-P30

Published: 1 May 2012

The voltage dependent N-type Ca2+ channel (NCC) distributed in the nerve ending of the central and peripheral nerves. NCC is considered as potential therapeutic target for several pathological disorders like neuropathic pain and stroke disease. For understanding mechanism of action at the atomic level crystal structure provide valuable inside but lack of crystal structure of ion channel lead sequence analysis of different types of voltage dependent Ca2+ channel (VDCC) and we found identical/similar active site residues, which was confirmed by site-directed mutagenesis analysis of L-type Ca2+ channel (LCC). Based on these observations, we have developed for the first time the homology model of the closed state of NCC receptor at the ligand-sensing region by using bacterial K+ channel receptor. Further, molecular docking using different dihydropyridine (DHP) blockers identified NCC receptor hot spot binding residues, which is in consonance with that of the LCC. These residues are potential for further biochemical investigations. To understand binding and stability behavior of NCC with the DHP (amlodipine) in closed state, 50 nano second molecular dynamics simulation in lipid bilayer membrane environment were carried out. This analysis revealed the closed state stabilizing by binding of ligand into inner part of S6 region.

Authors’ Affiliations

Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER)


© Pandey et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.