Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

52-POS Board 52 UNDERSTANDING ION SELECTIVITY OF THE GASTRIC PROTON PUMP H + , K + - ATPASE Hridya Valia Madapally ; Himanshu Khandelia 1 ; Kazuhiro Abe 2 ; 1 University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Odense, Denmark 2 Nagoya University, Cellular and Structural Physiology Institute, Nagoya, Japan H + , K + -ATPase protein is an ATP-powered ion pump that maintains acidity of the stomach by electroneutral exchange of H + and K + ions across the gastric lumen. Though Na + is present in higher concentration in the stomach than K + , H + , K + -ATPase binds to K + ions with high specificity. One of the main hypotheses attributes the selectivity of K + over Na + to the protonation states of specific negatively charged amino acids present at the binding site of the protein. Current experimental methods are incapable of accurately identifying the protonation states of these residues at the binding site. Hence, mutation of residues to mimic protonation were employed and the activity of the mutated proteins at different concentration of K + and Na + ions were measured. We also use free energy perturbation methods to find the potential protonated sites at the binding site that would favour K + binding over Na + binding. We perform alchemical transformations of K + ion at the binding site to Na + ion with different combinations of the protonated amino acids at the binding site to measure the free energy difference in binding of the two ions. We identify that the glutamic acid residues E343, E795 and E936 are protonated and preferentially ensures K + binding.

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