SOLVENT DIELECTRIC EFFECTS ON PROTEIN DYNAMICS
SOLVENT DIELECTRIC EFFECTS ON PROTEIN DYNAMICS
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DOI：
10.1073/pnas.89.11.5167
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发表时间：
1992-06-01
影响因子：
11.1
通讯作者：
CLARK, DS
中科院分区：
文献类型：
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作者：
AFFLECK, R;HAYNES, CA;CLARK, DS
采用电子顺磁共振（EPR）光谱和分子动力学（MD）模拟研究了α -凝乳胰蛋白酶在介电常数72 ~ 1.9范围内的动力学。EPR测量表明，随着溶剂介电常数的降低，两个自旋标记氨基酸（Met-192和Ser-195）附近的运动显著减少，这与蛋白质带电残基之间静电力的变化趋势一致。EPR结果和MD模拟显示，蛋白质的运动速率与本体溶剂的介电常数之间存在非常相似的功能依赖关系；然而，蛋白质原子的预测运动明显快于自旋标签的实际运动。介电常数为5和72的MD计算表明，在蛋白质的外表面附近差异最大。一般来说，在较低的介电常数下，蛋白质的许多原子移动得更慢，许多最慢的残基靠近外部。这些结果表明，动力学的改变可能会导致不寻常的性质-例如。修饰了酶在近干燥有机溶剂中的立体选择性。
Electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations were used to investigate the dynamics of alpha-chymotrypsin in solvents ranging in dielectric constant from 72 to 1.9. EPR measurements showed that motions in the vicinity of two spin-labeled amino acids (Met-192 and Ser-195) decreased dramatically with decreasing solvent dielectric constant, a trend consistent with changes in the electrostatic force between charged residues of the protein. EPR results and MD simulations revealed a very similar functional dependence between rates of motion in the protein and the dielectric constant of the bulk solvent; however, predicted motions of protein atoms were markedly faster than measured motions of the spin labels. MD calculations for dielectric constants of 5 and 72 showed the greatest differences near the outer surface of the protein. In general, at the lower dielectric constant many atoms of the protein move more slowly, and many of the slowest residues are near the exterior. These results suggest that altered dynamics may contribute to the unusual properties-e.g., modified stereoselectivities-of enzymes in nearly dry organic solvents.