Hassanali Ali A, Li Tanping, Zhong Dongping, Singer Sherwin J
Biophysics Program, Ohio State University, Columbus, Ohio 43210, USA.
J Phys Chem B. 2006 Jun 1;110(21):10497-508. doi: 10.1021/jp0601926.
We report studies of the structure and dynamics of a tripeptide Lys-Trp-Lys (KWK) in aqueous solution following photoexcitation by molecular dynamics simulations. For ground-state KWK, we observe three stable conformations with free energy differences of less than 5.2 kJ/mol. Each conformer is stabilized by a pi-cation interaction between one of three protonated amino groups and the indole moiety. For the excited state of tryptophan in KWK, the simulated molecular dynamics of the three isomers are similar, all in good agreement with recent femtosecond experiments (J. Phys. Chem. B 2005, 109, 16901). Specifically, we observe: (1) the fluorescence anisotropy is dominated by a single-exponential component and decays in approximately 130 ps, (2) the total dynamic Stokes shift reaches approximately 2700 cm(-1), and (3) the excited state relaxation dynamics occurs on several time scales ranging from femtoseconds to tens of picoseconds. The relaxation dynamics involve rapid initial response of neighboring water, followed by local motions of flexible peptide chains. These processes drive global restructuring of the tripeptide on a rather flat energy surface, inducing slower dynamics evident in both the water and protein contributions to the stabilization energy of the photoexcited chromophore. The water and protein dynamics are strongly correlated. On a still longer time scale, we observe isomerization of two excited state conformers to the other most stable one, an analogue for evolution of trajectories along the funnel on the rugged free energy landscape to the final "native" state. Our studies suggest new experiments to detect this unique dynamics.
我们通过分子动力学模拟报告了三肽赖氨酸-色氨酸-赖氨酸（KWK）在水溶液中光激发后的结构和动力学研究。对于基态KWK，我们观察到三种稳定构象，其自由能差小于5.2 kJ/mol。每个构象异构体都通过三个质子化氨基之一与吲哚部分之间的π-阳离子相互作用而稳定。对于KWK中色氨酸的激发态，三种异构体的模拟分子动力学相似，均与最近的飞秒实验（《物理化学杂志B》2005年，109卷，16901页）高度吻合。具体而言，我们观察到：（1）荧光各向异性由单指数成分主导，并在约130 ps内衰减；（2）总动态斯托克斯位移达到约2700 cm⁻¹；（3）激发态弛豫动力学发生在从飞秒到几十皮秒的几个时间尺度上。弛豫动力学涉及相邻水的快速初始响应，随后是柔性肽链的局部运动。这些过程在相当平坦的能量表面上驱动三肽的整体重构，导致在水和蛋白质对光激发发色团稳定能的贡献中都明显出现较慢的动力学。水和蛋白质的动力学密切相关。在更长的时间尺度上，我们观察到两个激发态构象异构体异构化为另一个最稳定的构象异构体，这类似于沿着崎岖自由能景观上的漏斗形轨迹向最终“天然”状态的演化。我们的研究提出了检测这种独特动力学的新实验。
