Folding Mechanism Of The Disordered Biodlogical Macromolecular Coupled Partener

Intrinsic disordered proteins have no stable 3D structures, and exist as loose andrandom structures. However, these proteins have normal biological function. Based on theestimation of biologist, about 27% to 41% of the eukaryotic proteins are intrinsicdisordered. Until recently, 643 proteins have been found the detailed structure information.Furthermore, these proteins undergo a transition from disordered to well folded uponbinding with a specific partner. Then they can specifically regulate relative biologicalprocess. Currently, there are two hypotheses on the folding mechanism of disorderedproteins coupled with binding partner. One is induced-fit, the other isconformational-selection. In our study, we performed explicit-solvent all atomic moleculardynamics (MD) simulation on three different systems to explore the folding mechanism ofdisordered biological macromolecular coupled with binding partner. First, we simulatedthe folding process of disordered protein TIS11dTZF coupled with mRNA. Second, weinvestigated the folding mechanism of disordered Brinker binding with DNA. Finally, weextended the study subject from disordered protein to intrinsic disordered nucleic acid.The folding process of the disordered snRNA coupled with U1A is followed by induced fitmechanism. Our simulation results are in good agreement with the previous experimentalobservations. The folding pathway of these complexes is changed upon the binding ofpartner. These studies can help us to insight into the folding kinetics of intrinsic disorderedbiomolecules coupled the binding of partners.