Salt Induced Transitions in the Conformational Ensembles of Intrinsically Disordered Proteins

Abstract

Salts modulate the behavior of intrinsically disordered proteins (IDPs). In low ionic strength solutions, IDP conformations are primarily perturbed by the screening of electrostatic interactions, independent of the identity of the salt. In this regime, insight into the IDP behavior can be obtained using the theory for salt-induced transitions in charged polymers. However, in high ionic strength solutions, salt-specific interactions with the charged and uncharged residues, known as the Hofmeister effect, influence IDP behavior. There is a lack of reliable theoretical models in high salt concentration regimes to predict the salt effect on IDPs. Using a coarse-grained simulation model for the IDPs and experimentally measured water to salt solution transfer free-energies of various chemical groups, we studied the salt-specific transitions induced in the IDPs conformational ensemble. We probed the effect of three different salts, ranging from protective osmolyte to denaturant, on five IDPs belonging to various polymer classes classified based on charge content. The transitions observed in the IDP conformational ensembles are dependent on the salt used and the IDP polymer class. An important implication of these results is that a suitable salt can be identified to induce condensation of an IDP through liquid-liquid phase separation.