Molecular dynamics simulations have been performed on the intrinsically disordered 39-residue N-terminal transactivation domain of p53 (p531-39). Simulations not only revealed that p531-39 is natively compact, but also possesses a folded structure. Furthermore, leucine-rich hydrophobic clusters were found to play a crucial role in the formation and stabilization of the folded structure of p531-39. Collapsing in the sub-microsecond timescale might allow for rapid conformational turnovers of p531-39, necessary for its efficient transactivation activity and modulation. Fast collapsing might be the result of unique conformational landscapes, featuring several energy minima separated by small energy barriers. It is suggested that IDPs with highly specialized functions in the cell, such as transactivation, possibly display more ordered patterns than their less specialized counterparts.
Bibliographical noteFunding Information:
The author was supported in part by grants from Barcelona Supercomputing Center and CONACYT. The author acknowledges the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center.
Copyright 2009 Elsevier B.V., All rights reserved.
- Intrinsically disordered protein
- Leucine-rich hydrophobic cluster
- Molecular dynamics simulation
- Protein folding
- p53 transactivation domain