A Chemical Perspective on Allostery

Much work has been done in the past decade to quantify the phenomenon of allosteric communication in proteins. Every new study unveils an extra piece of the puzzle in our search for an understanding of allostery that allows us to make predictions on the response of a protein to medically relevant stimuli such as pathological mutations or drug binding. This review summarizes recent advances in the analysis of mechanisms of allosteric communication in proteins, and combines this new knowledge to offer a perspective of allostery which is consistent with chemical views of molecular processes. First, we review recent work, particularly computational, on the characterization of signal propagation and conformational changes in allosteric proteins. We then compare different models of allostery, and discuss the significance of the concept of an allosteric pathway. We argue that allostery can be rationalized in terms of pathways of residues that efficiently transmit energy between different binding sites. We then provide examples that show how this picture could account for most of the observed data, since energy flow may be manifested as changes in both structure and dynamics. We conclude by acknowledging that the proposed view is still a simplification and should not be taken as a rigorous model of allosteric communication in proteins. Nevertheless, simple pictures like this can go a long way in improving our understanding of many complex phenomena observed in nature.