Allostery and structural dynamics in protein evolution

P. Campitelli, S. B. Ozkan

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationEvolution, Origin of Life, Concepts and Methods
PublisherSpringer International Publishing
Pages179-194
Number of pages16
ISBN (Electronic)9783030303631
ISBN (Print)9783030303624
DOIs
StatePublished - Oct 1 2019

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)

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