Conformational diversity and the emergence of sequence signatures during evolution.

Proteins' native structure is an ensemble of conformers in equilibrium, including all their respective functional states and intermediates. The induced-fit first and the pre-equilibrium theories later, described how structural changes are required to explain the allosteric and cooperative behaviours in proteins, which are key to protein function. The conformational ensemble concept has become a key tool in explaining an endless list of essential protein properties such as function, enzyme and antibody promiscuity, signal transduction, protein-protein recognition, origin of diseases, origin of new protein functions, evolutionary rate and order-disorder transitions, among others. Conformational diversity is encoded by the amino acid sequence and such a signature can be evidenced through evolutionary studies as evolutionary rate, conservation and coevolution.

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