Paper Citing NAMD - Abstract
Moran, Oscar; Grottesi, Alessandro; Chadbum, Andrew J.; Tammaro, Paolo
Parametrisation of the free energy of ATP binding to wild-type and mutant Kir6.2 potassium channels
BIOPHYSICAL CHEMISTRY, 171:76-83, JAN 2013
ATP-sensitive K+ (K-ATP) channels, comprised of pore-forming Kir6.x and regulatory SURx subunits, play important roles in many cellular functions; because of their sensitivity to inhibition by intracellular ATP, K-ATP channels provide a link between cell metabolism and membrane electrical activity. We constructed structural homology models of Kir62 and a series of Kir62 channels carrying mutations within the putative ATP-binding site. Computational docking was carried out to determine the conformation of ATP in its binding site. The Linear Interaction Energy (LIE) method was used to estimate the free-energy of ATP binding to wild-type and mutant Kir62 channels. Comparisons of the theoretical binding free energies for ATP with those determined from mutational experiments enabled the identification of the most probable conformation of ATP bound to the Kir6.2 channel. A set of LIE parameters was defined that may enable prediction of the effects of additional Kir62 mutations within the ATP binding site on the affinity for ATP. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.
