Transmembrane ion pumping proteins such as the Na+, K+, ATPase and the gastric H+,K+, ATPase use chemical energy for the uphill transport of ions across cellular membranes. Life is unsustainable without pumps and their partial impairment causes disease. We use MD simulations to investigate ion pumps both in their natural electrical and thermal environments on the molecular level, to investigate mechanisms of ion selectivity, ion pathways and ion stoichiometry.

The Na+ K+ Pump Embedded in a Lipid Bilayer with 3 Na+ ions bound. The simulations were used to determine the protonation states of acidic amino acids in the ion-binding site

Representative Publications

Na+, K+, ATPase

Poulsen, H., Khandelia, H., Morth, J.P., Bublitz, M., Mouritsen, O.G., Egebjerg, J. and Nissen, P. (2010) Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase. Nature, 467, 99-102. DOI: 10.1038/nature09309

Poulsen, H., Nissen, P., Mouritsen, O. G., and Khandelia, H. (2012) Protein Kinase A (PKA) Phosphorylation of Na+/K+-ATPase Opens Intracellular C-terminal Water Pathway Leading to Third Na+-binding site in Molecular Dynamics Simulations, J. Biol. Chem. 287, 15959-15965.

Kopec, W., Loubet, B., Poulsen, H., and Khandelia, H. (2014) Molecular mechanism of Na(+),K(+)-ATPase malfunction in mutations characteristic of adrenal hypertension, Biochemistry 53, 746-754.


Sahoo, S. K., Shaikh, S. A., Sopariwala, D. H., Bal, N. C., Bruhn, D. S., Kopec, W., Khandelia, H., and Periasamy, M. (2015) The N Terminus of Sarcolipin Plays an Important Role in Uncoupling Sarco-endoplasmic Reticulum Ca2+-ATPase (SERCA) ATP Hydrolysis from Ca2+ Transport, J. Biol. Chem. 290, 14057-14067.

H+, K+, ATPase

Dubey, V., Han, M., Kopec, W., Solov’yov, I. A., Abe, K., and Khandelia, H. (2018) K(+) binding and proton redistribution in the E2P state of the H(+), K(+)-ATPase, Sci. Rep. 8, 12732.

Yamamoto, K., Dubey, V., Irie, K., Nakanishi, H., Khandelia, H., Fujiyoshi, Y., and Abe, K. (2019) A single K(+)-binding site in the crystal structure of the gastric proton pump, Elife 8.