Publication Type:

Journal Article


Molecular Informatics, Volume 31, Number 9, p.643-657 (2012)



amlodipine, article, binding site, calcium channel blocking agent, calcium channel N type, calcium channel N type receptor, calcium ion, cilnidipine, drug mechanism, drug potency, drug receptor binding, hydrophobicity, ion permeability, membrane receptor, molecular docking, molecular model, nifedipine, pharmacological blocking, priority journal, protein domain, receptor blocking, unclassified drug


<p>The voltage dependent N-type Ca2+ channel (NCC) receptor was identified to have therapeutic potential for the treatment of neuropathic pain and stroke disease. The Ca2+ ion transport through the transmembrane influx is mainly dependent on the closing, opening, or intermediate state gating mechanism of NCC. Harnessing this dynamic gating mechanism at the structural level is an important and challenging physiological phenomenon. The three dimensional (3D) structure of this membrane receptor is not yet experimentally determined to understand its mechanism of action. Based on these observations, we have developed for the first time the structure of the closed state of the NCC receptor at the pore forming domains which mainly involve three transmembrane helices (TMhs) S5, P and S6. Hot-spot binding site residues of this receptor model were identified by molecular docking technique using amlodipine, cilnidipine and nifedipine compounds known to be potent Ca 2+ channel antagonists. Further, the Ca2+ ion permeability and the hydrophobic gating mechanism provided better structural and functional insights on the NCC receptor. These results are in consonance with other Ca 2+ channel receptors and would provide guidance for further biochemical investigations. Copyright © 2012 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.</p>


cited By (since 1996)1

Cite this Research Publication

Aab Pandey, P, Jab, Tripathi, S., and Mohan, Cab Gopi, “Harnessing human N-type Ca2+ channel receptor by identifying the atomic hotspot regions for its structure-based blocker design”, Molecular Informatics, vol. 31, pp. 643-657, 2012.