Abstract
The sequence-structure-function paradigm for proteins has been well accepted in the scientific community. However, with the emergence of the ensemble view of proteins, it has become clear that this fails to incorporate the importance of protein dynamics, which we now understand govern the underlying function of proteins. Here, we introduce two tools—the dynamic flexibility index (DFI) and the dynamic coupling index (DCI) which can quantify structural flexibility and dynamic coupling at a site-specific, single amino acid level. We show that it is possible to relate evolutionary conservation to amino acid flexibility and that disease-associated protein variants coincide with mutations at rigid positions within a protein. In combination with experimental data, we also capture important changes in structural conformation that coincide with the evolution of protein function through changes in structural dynamics. Finally, we discuss how nature can modulate change through allosteric mutations which alter the internal interaction network of proteins, and how changes in allosteric regulation can result in disease phenotypes.
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Campitelli, P., Ozkan, S.B. (2019). Allostery and Structural Dynamics in Protein Evolution. In: Pontarotti, P. (eds) Evolution, Origin of Life, Concepts and Methods. Springer, Cham. https://doi.org/10.1007/978-3-030-30363-1_9
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DOI: https://doi.org/10.1007/978-3-030-30363-1_9
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