Probing coupled conformational transitions of intrinsically disordered proteins in their interactions with target proteins

Abstract

Intrinsically disordered proteins or regions (IDPs or IDRs) are abundant in the eukaryotic proteome and critical in regulation of dynamic cellular processes. Intensive structural investigations have proposed the molecular mechanisms of the interaction between IDRs and their binding partners. Here we extract the distinct thermodynamic features of coupled conformational transitions of IDRs founding the interaction mechanisms. We also present simulation tools to facilitate a design of the calorimetric experiments probing and quantifying the conformational transitions of IDRs. The suggested thermodynamic approach will further advance our understanding of distribution among multiple states of IDRs in their interactions with target molecules.