Binding induced intrinsically disordered protein folding with molecular dynamics simulation

Abstract

Intrinsically disordered proteins lack stable tertiary and/or secondary structures under physiological conditions in vitro. Intrinsically disordered proteins undergo significant conformational transitions to well folded forms only on binding to partner. Molecular dynamics simulations are used to research the mechanism of folding for intrinsically disordered protein upon partner binding. Room-temperature MD simulations suggest that the intrinsically disordered proteins have non-specific and specific interactions with the partner. Kinetic analysis of high-temperature MD simulations shows that bound and apo-states unfold via a two-state process, respectively. θ-value analysis can identify the key residues of intrinsically disordered proteins. Kolmogorov-Smirnov (KS) P test analysis illustrates that the specific recognition between intrinsically disordered protein and partner might follow induced-fit mechanism. Furthermore, these methods can be widely used for the research of the binding induced folding for intrinsically disordered proteins.