Conformational entropy in molecular recognition of intrinsically disordered proteins.

Broad conformational ensembles make intrinsically disordered proteins or regions entropically intriguing. Although methodologically challenging and understudied, emerging studies into their changes in conformational entropy (ΔS°) upon complex formation have provided both quantitative and qualitative insight. Recent work based on thermodynamics from isothermal titration calorimetry and NMR spectroscopy uncovers an expanded repertoire of regulatory mechanisms, where ΔS° plays roles in partner selection, state behavior, functional buffering, allosteric regulation, and drug design. We highlight these mechanisms to display the large entropic reservoir of IDPs for the regulation of molecular communication. We call upon the field to make efforts to contribute to this insight as more studies are needed for forwarding mechanistic decoding of intrinsically disordered proteins and their complexes.