DYNAMICS OF LIGAND ESCAPE FROM THE HEME POCKET OF MYOGLOBIN
DYNAMICS OF LIGAND ESCAPE FROM THE HEME POCKET OF MYOGLOBIN
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DOI：
10.1021/ja00231a018
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发表时间：
1988-11-09
影响因子：
15
通讯作者：
CASE, DA
中科院分区：
文献类型：
--
作者：
KOTTALAM, J;CASE, DA
分子动力学计算用于研究双氧配体离开抹香鲸肌红蛋白血红素袋的过程的动力学。伞采样技术用于在多个温度下生成自由能分布，以便沿着远端组氨酸和缬氨酸残基之间的路径逃逸，并且探索了评估此类分布的统计精度的方法。结果用于计算过渡态近似和完整经典动力学中配体逃逸的速率常数。对于该过程，过渡态理论速率（即传输系数）的修正范围为 0.8 至 0.9，并且计算出的室温速率常数与实验非常吻合。接近室温时，计算出的活化能小于 1 kcal/mol，但在较低温度（180 至 270 K 之间）时，活化能升至 5 kcal/mol。根据伴随配体逃逸的蛋白质波动模型讨论了这种非阿累尼乌斯温度依赖性的潜在物理起源。
Molecular dynamics calculations are used to study the kinetics of the process by which a dioxygen ligand leaves the heme pocket of sperm whale myoglobin. Umbrella sampling techniques are used to generate free-energy profiles at several temperatures for escape along a path between the distal histidine and valine residues, and methods for assessing the statistical precision of such profiles are explored. The results are used to compute rate constants for ligand escape, both in the transition-state approximation and with full classical dynamics. Corrections to transition-state theory rates (i.e., the transmission coefficients) are in the range 0.8 to 0.9 for this process, and the computed rate constants at room temperature are in good agreement with experiment. Near room temperature the computed activation energy is less than 1 kcal/mol, but at lower temperatures (between 180 and 270 K) this rises to 5 kcal/mol. Potential physical origins of such non-Arrhenius temperature dependence are discussed in light of models of protein fluctuations that accompany ligand escape.