Folding lambda-repressor at its speed limit.
We show that the five-helix bundle lambda(6-85) can be engineered and solvent-tuned to make the transition from activated two-state folding to downhill folding. The transition manifests itself as the appearance of additional dynamics faster than the activated kinetics, followed by the disappearance of the activated kinetics when the bias toward the native state is increased. Our fastest value of 1 micros for the "speed" limit of lambda(6-85) is measured at low concentrations of a denaturant that smooths the free-energy surface. Complete disappearance of the activated phase is obtained in stabilizing glucose buffer. Langevin dynamics on a rough free-energy surface with variable bias toward the native state provides a robust and quantitative description of the transition from activated to downhill folding. Based on our simulation, we estimate the residual energetic frustration of lambda(6-85) to be delta(2) G approximately 0.64 k(2)T(2). We show that lambda(6-86), as well as very fast folding proteins or folding intermediates estimated to lie near the speed limit, provide a better rate-topology correlation than proteins with larger energetic frustration. A limit of beta > or = 0.7 on any stretching of lambda(6-85) barrier-free dynamics suggests that a low-dimensional free-energy surface is sufficient to describe folding.
Yang
Wei Yuan
WY
Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 61801, USA.
Gruebele
Martin
M
D002942:Circular Dichroism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D014783:Viscosity
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D005947:Glucose