Exploring the functions of hydrophilic channels in cytochrome oxidase by computational and biophysical methods.


Cytochrome c oxidase is a key energy-conserving respiratory protein that couples the complex task of reduction of oxygen to water with harnessing of the associated released energy to proton pumping across the membrane in which it resides. The aim will be to investigate with computational methods hydrophilic channels within the protein to distinguish which act as channels for proton pumping and which can be modulated by external factors (such as ligand binding or phosphorylation changes) to control function. Predictions from the computational work will be tested by mechanistic biophysical studies of specific protein variants in the laboratory of the secondary supervisor.


P.R. Rich, A. Maréchal, "Functions of the hydrophilic channels in protonmotive cytochrome c oxidase", J. R. Soc. Interface. 10 (2013) 1.


M. Wikström, M.I. Verkhovsky, G. Hummer, "Water-gated mechanism of proton translocation by cytochrome c oxidase", Biochim. Biophys. Acta 1604 (2003) 61.


A. Maréchal, P.R. Rich, "Water molecule reorganization in cytochrome c oxidase revealed by FTIR spectroscopy", Proc. Natl. Acad. Sci. USA 108 (2011) 8634.


E. Rosta, W. Yang, G. Hummer, "Calcium inhibition of Ribonuclease H1 two-metal ion catalysis", J. Am. Chem. Soc., 136 (2014) 3137.


E. Rosta, G. Hummer, "Free Energies from Dynamic Weighted Histogram Analysis Using Unbiased Markov State Model", J. Chem. Theor. Comp. 11 (2015) 276.

Biological Areas:

Structural Biology
Chemical Biology


Molecules, cells and industrial biotechnology