Multi-scale ensemble modeling of modular proteins with intrinsically disordered linker regions: application to p53.

ABSTRACT: In eukaryotic proteins, intrinsically disordered regions (IDRs) are ubiquitous and often exist in linker regions that flank the functional domains of modular proteins, regulating their functions. For detailed structural ensemble modeling of IDRs, we propose a multiscale method for IDRs that possess significant long-range order in modular proteins and apply it to the eukaryotic transcription factor p53 as an example. First, we performed all-atom (AA) molecular dynamics (MD) simulations of the explicitly solvated p53 linker region, without experimental restraint terms, finding fractional long-range contacts within the linker. Second, we fed this AA MD ensemble into a coarse-grained (CG) model, finding an optimal set of contact potentials. The optimized CG MD simulations reproduced the contac

SUBMITTER: Terakawa T 

PROVIDER: S-EPMC4129485 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature