TY - JOUR
T1 - Protein dielectric constants determined from NMR chemical shift perturbations
AU - Kukic, Predrag
AU - Farrell, Damien
AU - McIntosh, Lawrence P.
AU - García-Moreno E., Bertrand
AU - Jensen, Kristine Steen
AU - Toleikis, Zigmantas
AU - Teilum, Kaare
AU - Nielsen, Jens Erik
PY - 2013/11/13
Y1 - 2013/11/13
N2 - 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 (εeff and εp) required in Coulombic 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 14 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) ranged from 2 to 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.
AB - 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 (εeff and εp) required in Coulombic 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 14 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) ranged from 2 to 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.
U2 - 10.1021/ja406995j
DO - 10.1021/ja406995j
M3 - Journal article
C2 - 24124752
SN - 0002-7863
VL - 135
SP - 16968
EP - 16976
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 45
ER -