On Modulating the Regulatory Role of Intrinsically Disordered Proteins Using Small Molecules

Abstract

Intrinsically disordered regions (IDRs) in proteins play a variety of critical roles in complex regulatory networks of higher organisms. Most importantly, perhaps, is that they are necessary to provide specificity in promiscuous interactions. I will show that both the specificity of IDRs for their targets and their entropy loss upon binding are essential to provide discrimination among similar physical interactions. Attempts to temper with this class of interacting proteins using small molecules will necessarily comprise densely functionalized compounds. Implications for the challenges involve in the rational design of small molecules targeting IDRs will be discussed.