Mechanistic Insights from Replica Exchange Molecular Dynamics Simulations into Mutation Induced Disordered-to-Ordered Transition in Hahellin, a βγ-Crystallin

Intrinsically disordered proteins (IDPs) form a special category because they lack a unique well-folded 3D structure under physiological conditions. They play crucial role in cell signaling and regulatory functions and are responsible for several diseases. Although they are abundant in nature, only a small fraction of them have been characterized until date. Such proteins adopt a range of conformations and can undergo transformation from disordered-to-ordered state or vice versa upon binding to ligand. Insights of such conformational transition is perplexing in several cases. In the present study, we characterized disordered as well as ordered states and the interactions contributing the transitions through a mutational study by employing replica exchange molecular dynamics simulation with generalized Born implicit solvent model on a protein from the βγ-crystallin superfamily. Most of the proteins within this superfamily are inherently ordered and highly stable. However, Hahellin, although a member of the...