Graphs of dynamic H-bond networks: from model proteins to protein complexes in cell signaling.

Proton transfer reactions are ubiquitous in biology, as they are involved in the functioning of numerous proteins. Studies of model proteins have revealed mechanisms by which proteins use hydrogen-bond networks for proton transfers, and couple proton transfers with protein and water dynamics. In this review we focus on graph-based analyses of dynamic hydrogen-bond networks at membrane interfaces, protein H-bond networks for allosteric conformational coupling and pH sensitivity, and challenges in extrapolating from knowledge acquired from studies of model membrane proteins to computational studies of macro-molecular protein complexes that are part of cell signaling networks directly relevant to the development of new therapeutics.