title: Tryptophan-47 rotational isomerization in variant-3 scorpion neurotoxin. A combination thermodynamic perturbation and umbrella sampling study.
abstract: A combination thermodynamic perturbation and umbrella sampling study predicts two free energy wells for the rotational isomerization of the variant-3 scorpion neurotoxin tryptophan-47 indole side chain. One well has the indole side chain in the crystallographic orientation; the other has the indole rotated approximately 220 degrees to form a new conformation with a relative free energy of 3 +/- 2 kcal/mol. The activation barrier is 8.5 kcal/mol from the crystallographic well, from which transition state theory predicts a rate of escape of 2 x 10(5) s-1. Correlations in the displacements of side chains neighboring tryptophan-47 and the isomerization reaction coordinate last up to 20 ps. Favorable conditions of experimental verification are discussed.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905.
authors.forename: C
authors.initials: C
authors.lastname: Haydock
authors.forename: J C
authors.initials: JC
authors.lastname: Sharp
authors.forename: F G
authors.initials: FG
authors.lastname: Prendergast
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D014644:Genetic Variation; D007536:Isomerism; D008433:Mathematics; D008962:Models, Theoretical; D011336:Probability; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000235:genetics; D013816:Thermodynamics; D014364:Tryptophan
chemical_list: D012604:Scorpion Venoms; D014364:Tryptophan