title: Simulations of tryptophan fluorescence dynamics during folding of the villin headpiece.
abstract: Protein folding kinetics is commonly monitored by changes in tryptophan (Trp) fluorescence intensity. Considerable recent discussion has centered on whether the fluorescence of the single Trp in the much-studied, fast-folding villin headpiece C-terminal domain (HP35) accurately reflects folding kinetics, given the general view that quenching is by a histidine cation (His(+)) one turn away in an α-helix (helix III) that forms early in the folding process, according to published MD simulations. To help answer this question, we ran 1.0 μs MD simulations on HP35 (N27H) and a faster-folding variant in its folded form at 300 K and used the coordinates and force field charges with quantum calculations to simulate fluorescence quenching caused by electron transfer to the local amide and to the His(+). The simulations demonstrate that quenching by His(+) in the fully formed helix III is possible only during certain Trp and His(+) rotamer and solvent conformations, the propensity of which is a variable that can allow Trp fluorescence to report the global folding rate, as recent experiments imply.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717-3400, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Tusell
authors.forename: Patrik R
authors.initials: PR
authors.lastname: Callis
mesh_terms: D005453:Fluorescence; D008840:Microfilament Proteins / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D008840:Microfilament Proteins; C026615:villin; D014364:Tryptophan