The sequence-structure-function paradigm has dominated twentieth century molecular
biology. The paradigm tacitly stipulated that for each sequence there exists a single, well …

This thematic issue focuses on allostery and protein ensembles the populations of
conformational states which constitute their physical foundation. The awareness of the …

Conspectus Are all protein interactions fully optimized? Do suboptimal interactions
compromise specificity? What is the functional impact of frustration? Why does evolution not …

All soluble proteins populate conformational ensembles that together constitute the native
state. Their fluctuations in water are intrinsic thermodynamic phenomena, and the …

It is now well-known that proteins exist at equilibrium as ensembles of conformational states
rather than as unique static structures. Here we review from an ensemble perspective …

Highlights•Protein's native structure is an ensemble of conformers with similar energies.•
Conformational diversity constraints sequence divergence.•High conformational diversity …

Highlights•Intrinsic dynamics plays a major role in enabling protein interactions.•Soft/global
modes of motions facilitate binding and assembly.•Soft modes define pre-existing pathways …

Functioning proteins do not remain fixed in a unique structure, but instead they sample a
range of conformations facilitated by motions within the protein. Even in the native state, a …

Whereas previously we have successfully utilized the folding funnels concept to rationalize
binding mechanisms (Ma B, Kumar S, Tsai CJ, Nussinov R, 1999, Protein Eng 12: 713–720) …

Protein sequence, structure, and function are inherently linked through evolution and
population genetics. Our knowledge of protein structure comes from solved structures in the …