Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations

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• 作者：Predrag Kukic ; Damien Farrell ; Lawrence P. McIntosh ; Bertrand Garc铆a-Moreno E. ; Kristine Steen Jensen ; Zigmantas Toleikis ; Kaare Teilum ; Jens Erik Nielsen
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：November 13, 2013
• 年：2013
• 卷：135
• 期：45
• 页码：16968-16976
• 全文大小：355K
• 年卷期：v.135,no.45(November 13, 2013)
• ISSN：1520-5126

文摘

Understanding the connection between protein structure and function requires a quantitative understanding of electrostatic effects. Structure-based electrostatic calculations are essential for this purpose, but their use has been limited by a long-standing discussion on which value to use for the dielectric constants (蔚_eff and 蔚_p) required in Coulombic and Poisson鈥揃oltzmann models. The currently used values for 蔚_eff and 蔚_p are essentially empirical parameters calibrated against thermodynamic properties that are indirect measurements of protein electric fields. We determine optimal values for 蔚_eff and 蔚_p by measuring protein electric fields in solution using direct detection of NMR chemical shift perturbations (CSPs). We measured CSPs in 14 proteins to get a broad and general characterization of electric fields. Coulomb鈥檚 law reproduces the measured CSPs optimally with a protein dielectric constant (蔚_eff) from 3 to 13, with an optimal value across all proteins of 6.5. However, when the water鈥損rotein interface is treated with finite difference Poisson鈥揃oltzmann calculations, the optimal protein dielectric constant (蔚_p) ranged from 2 to 5 with an optimum of 3. It is striking how similar this value is to the dielectric constant of 2鈥? measured for protein powders and how different it is from the 蔚_p of 6鈥?0 used in models based on the Poisson鈥揃oltzmann equation when calculating thermodynamic parameters. Because the value of 蔚_p = 3 is obtained by analysis of NMR chemical shift perturbations instead of thermodynamic parameters such as pK_a values, it is likely to describe only the electric field and thus represent a more general, intrinsic, and transferable 蔚_p common to most folded proteins.