Haydock C, Sharp J C, Prendergast F G
Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905.
Biophys J. 1990 Jun;57(6):1269-79. doi: 10.1016/S0006-3495(90)82645-X.
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.
一项结合热力学微扰和伞形采样的研究预测，变异型3蝎神经毒素色氨酸-47吲哚侧链的旋转异构化存在两个自由能阱。一个阱中吲哚侧链处于晶体学取向；另一个阱中吲哚旋转了约220度，形成了一个相对自由能为3±2千卡/摩尔的新构象。从晶体学阱出发的活化能垒为8.5千卡/摩尔，根据过渡态理论预测逃逸速率为2×10⁵ 秒⁻¹。与色氨酸-47相邻的侧链位移与异构化反应坐标之间的相关性持续长达20皮秒。文中还讨论了实验验证的有利条件。
