In continuum electrostatics the protein dielectric constant (ep) accounts for the response of the media to charge changes.  It is unclear what is the best or the correct value. The pKas of 75,000 ionizable residues in 800 proteins were determined as a function of ep using MCCE. The pKas of surface residues are generally independent of ep due to solvent exposure. For buried residues decreasing ep raises the desolvation penalty, favoring neutralization, but also increases the electrostatic pair-wise interactions, that usually favor ionization. The balance between these energies in response to changing ep leads to a small overall dependence of pKa on ep.  This relative independence helps explain why previous studies have not established a consistent value for ep.  The way that a relatively ep independent pKa reduces the impact of structural fluctuations on protein stability will be discussed.

Role of protein fluctuations, described by the dielectric constant, on pK<sub>a</sub>s of buried residues

244th National Meeting (2012)

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Role of protein fluctuations, described by the dielectric constant, on pKas of buried residues

Role of protein fluctuations, described by the dielectric constant, on pK_as of buried residues