Protein dielectric constants determined from NMR chemical shift perturbations.
Protein dielectric constants determined from NMR chemical shift perturbations.
复制标题
由NMR化学位移扰动确定的蛋白介电常数。
DOI：
10.1021/ja406995j
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发表时间：
2013-11-13
影响因子：
15
通讯作者：
Nielsen JE
中科院分区：
文献类型：
--
作者：
Kukic P;Farrell D;McIntosh LP;García-Moreno E B;Jensen KS;Toleikis Z;Teilum K;Nielsen JE
要了解蛋白质结构和功能之间的联系，需要对静电效应有一个定量的了解。基于结构的静电学计算对于这一目的是必不可少的，但它们的使用一直受到一个长期讨论的限制，即库仑模型和泊松-玻尔兹曼模型中所需的介电常数(εef和εp)应该使用哪个值。目前使用的εef和εp的值基本上是根据热力学性质校准的经验参数，热力学性质是蛋白质电场的间接测量。我们通过直接检测核磁共振化学位移微扰(CSP)来测量溶液中的蛋白质电场，从而确定εff和εp的最佳值。我们测量了14种蛋白质中的CSP，以获得电场的广泛和一般特征。库仑定律最佳地再现了测得的CSP，其蛋白质介电常数(εef)为3到13，所有蛋白质的最佳值为6.5.然而，当用有限差分泊松-玻尔兹曼方法处理水-蛋白质界面时，蛋白质的最佳介电常数(ε_p)范围为2-5，最佳介电常数为3。令人惊讶的是，该值与蛋白质粉末的介电常数2-4非常相似，而与根据泊松-玻尔兹曼方程计算热力学参数时模型中所用的ε_p为6-20有很大的不同。由于εp=3的值是通过分析核磁共振化学位移扰动而不是热力学参数(如pKa值)获得的，因此它可能只描述电场，因此代表了大多数折叠蛋白质所共有的更一般的、内在的和可转移的εp。
Understanding the connection between protein structure and function requires a quantitative understanding of electrostatic effects. Structure-based electrostatics calculations are essential for this purpose, but their use have been limited by a long-standing discussion on which value to use for the dielectric constants (εeff and εp) required in Coulombic models and Poisson-Boltzmann models. The currently used values for εeff and εp are essentially empirical parameters calibrated against thermodynamic properties that are indirect measurements of protein electric fields. We determine optimal values for εeff and εp by measuring protein electric fields in solution using direct detection of NMR chemical shift perturbations (CSPs). We measured CSPs in fourteen proteins to get a broad and general characterization of electric fields. Coulomb's law reproduces the measured CSPs optimally with a protein dielectric constant (εeff) from 3 to 13, with an optimal value across all proteins of 6.5. However, when the water-protein interface is treated with finite difference Poisson-Boltzmann calculations, the optimal protein dielectric constant (εp) rangedsfrom 2-5 with an optimum of 3. It is striking how similar this value is to the dielectric constant of 2-4 measured for protein powders, and how different it is from the εp of 6-20 used in models based on the Poisson-Boltzmann equation when calculating thermodynamic parameters. Because the value of εp = 3 is obtained by analysis of NMR chemical shift perturbations instead of thermodynamic parameters such as pKa values, it is likely to describe only the electric field and thus represent a more general, intrinsic, and transferable εp common to most folded proteins.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
2.9
作者：
BASHFORD, D;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
2.9
作者：
Hernandez, Griselda;Anderson, Janet S.;LeMaster, David M.
通讯作者：
LeMaster, David M.
影响因子：
2.2
作者：
AUGSPURGER, J;PEARSON, JG;SCHWARTZ, D
通讯作者：
SCHWARTZ, D
蛋白质功能的调节：晶体堆积界面和构象二聚化
影响因子：
2.9
作者：
Crowley, Peter B.;Matias, Pedro M.;Dennison, Christopher
通讯作者：
Dennison, Christopher