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Influence of pK a Shifts on the Calculated Dipole Moments of Proteins

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Abstract

The protein dipole moment is a low-resolution parameter that characterizes the second-order charge organization of a biomolecule. Theoretical approaches to calculate protein dipole moments rely on pK a values, which are either computed individually for each ionizable residue or obtained from model compounds. The influence of pK a shifts are evaluated first by comparing calculated and measured dipole moments of β-lactoglobulin. Second, calculations are made on a dataset of 66 proteins from the Protein Data Bank, and average differences are determined between dipole moments calculated with model pK as, pK as derived using a Poisson–Boltzmann approach, and empirically-calculated pK as. Dipole moment predictions that neglect pK a shifts are consistently larger than predictions in which they are included. The importance of pK a shifts are observed to vary with protein size, internal permittivity, and solution pH.

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Abbreviations

β-Lg:

β-Lactoglobulin

\( \Updelta {\text{p}}K_{\text{a}}^{\text{calc}} \) :

Calculated pK a shift

\( \mu_{{}} \) :

Dipole moment

\( \mu_{\text{m}} \) :

Dipole moment calculated using \( {\text{p}}K_{\text{a}}^{\text{m}} {\text{s}} \)

\( \mu_{\text{pb}} \) :

Dipole moment calculated using \( {\text{p}}K_{\text{a}}^{\text{pb}} {\text{s}} \)

B :

Estimation bias

D :

Average percentage difference

DNA:

Deoxyribonucleic acid

NMR:

Nuclear magnetic resonance

PDB:

Protein data bank

pI:

Isoelectric point

\( {\text{p}}K_{\text{a}}^{\text{calc}} \) :

Calculated pK a

\( {\text{p}}K_{\text{a}}^{\text{e}} \) :

Empirically-calculated pK a

\( {\text{p}}K_{\text{a}}^{\text{m}} \) :

Model pK a

\( {\text{p}}K_{\text{a}}^{\text{pb}} \) :

PoissonBoltzmann calculated pK a

RNase A:

Ribonuclease A

Z :

Formal charge of the ion

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Correspondence to Brett L. Mellor.

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Mellor, B.L., Khadka, S., Busath, D.D. et al. Influence of pK a Shifts on the Calculated Dipole Moments of Proteins. Protein J 30, 490–498 (2011). https://doi.org/10.1007/s10930-011-9355-8

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Keywords

  • Protein electrostatics
  • pK a shifts
  • Dielectric spectroscopy
  • Poisson–Boltzmann
  • Permittivity