کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5371193 | 1503939 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Parametrisation of the free energy of ATP binding to wild-type and mutant Kir6.2 potassium channels Parametrisation of the free energy of ATP binding to wild-type and mutant Kir6.2 potassium channels](/preview/png/5371193.png)
ATP-sensitive K+ (KATP) 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, KATP channels provide a link between cell metabolism and membrane electrical activity. We constructed structural homology models of Kir6.2 and a series of Kir6.2 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 Kir6.2 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 Kir6.2 mutations within the ATP binding site on the affinity for ATP.
Highlights⺠Structural homology models of wild-type and mutant Kir6.2 channels were developed. ⺠ATP binding free-energies were estimated with Linear Interaction Energy (LIE) method. ⺠Theoretically and experimentally determined ATP binding free energies were compared. ⺠This analysis leads to the identification of the conformation of ATP bound to Kir6.2. ⺠LIE parametrisation allows prediction of effects of Kir6.2 mutations on ATP affinity.
Journal: Biophysical Chemistry - Volume 171, January 2013, Pages 76-83