The origin of nonmonotonic complex behavior and the effects of nonnative interactions on the diffusive properties of protein folding.
We present a method for calculating the configurational-dependent diffusion coefficient of a globular protein as a function of the global folding process. Using a coarse-grained structure-based model, we determined the diffusion coefficient, in reaction coordinate space, as a function of the fraction of native contacts formed Q for the cold shock protein (TmCSP). We find nonmonotonic behavior for the diffusion coefficient, with high values for the folded and unfolded ensembles and a lower range of values in the transition state ensemble. We also characterized the folding landscape associated with an energetically frustrated variant of the model. We find that a low-level of frustration can actually stabilize the native ensemble and increase the associated diffusion coefficient. These findings can be understood from a mechanistic standpoint, in that the transition state ensemble has a more homogeneous structural content when frustration is present. Additionally, these findings are consistent with earlier calculations based on lattice models of protein folding and more recent single-molecule fluorescence measurements.
Oliveira
Ronaldo J
RJ
Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, Brazil.
Whitford
Paul C
PC
Chahine
Jorge
J
Wang
Jin
J
Onuchic
José N
JN
Leite
Vitor B P
VB
D000596:Amino Acids; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D004058:Diffusion; D019277:Entropy; D008958:Models, Molecular; D017510:Protein Folding; D013696:Temperature; D020124:Thermotoga maritima / Q000378:metabolism*
D000596:Amino Acids; D001426:Bacterial Proteins