Frustration and folding of a TIM barrel protein
Year: 2019
Type: article
Abstract: indole-3-glycerol phosphate synthase TIM barrel that appears within 50 μs and must at least partially unfold to achieve productive folding. Simulations reveal the presence of a major and 2 minor folding channels not detected in experiments. Frustration in folding, i.e., backtracking in native contacts, is observed in the major channel at the initial stage of folding, as well as late in folding in a minor channel before the appearance of the native conformation. Similarities in global and pairwise dimensions of the early intermediate, the formation of structure in the central region that spreads progressively toward each terminus, and a similar rate-limiting step in the closing of the β-barrel underscore the value of combining simulation and experiment to unravel complex folding mechanisms at the molecular level.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1017699072, G107546177, IDBR Type A: Optimization of microsecond mixing devices for biological kinetics via simulation and experiment, G1313983767, G1555076680, G1664757510, G2008846556, The Biophysics Collaborative Access Team, G2287611682, G262962599, G2853440140, G3075337988, G3961716793, G409777406, G4403145024, G498139845, G513797252, G5499275266, G5607048534, Multiscale Modeling and Enhanced Sampling of Protein-Protein Recognition, G6397724416, Advanced Pixel Array Detector for Time-Resolved SAXS and Fiber Diffraction, G6848031779, G6918803902, G7532037738, G7701581323, G8790389605, G9000178366, G9000275877, G969889393, G993149817
OpenAlex ID: W2963954598