title: The fast and the slow: folding and trapping of λ6-85.
abstract: Molecular dynamics simulations combining many microsecond trajectories have recently predicted that a very fast folding protein like lambda repressor fragment λ(6-85) D14A could have a slow millisecond kinetic phase. We investigated this possibility by detecting temperature-jump relaxation to 5 ms. While λ(6-85) D14A has no significant slow phase, two even more stable mutants do. A slow phase of λ(6-85) D14A does appear in mild denaturant. The experimental data and computational modeling together suggest the following hypothesis: λ(6-85) takes only microseconds to reach its native state from an extensively unfolded state, while the latter takes milliseconds to reach compact β-rich traps. λ(6-85) is not only thermodynamically but also kinetically protected from reaching such "intramolecular amyloids" while folding.
authors: Department of Chemistry and Center for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois 61801, USA.
authors: Maxim B
authors: MB
authors: Prigozhin
authors: Martin
authors: M
authors: Gruebele
mesh_terms: D010582:Bacteriophage lambda / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics; D013696:Temperature; D013816:Thermodynamics; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins