Empirical calculation of the relative free energies of peptide binding to the molecular chaperone DnaK

We describe a methodology to calculate the relative free energies of protein‐peptide complex formation. The interaction energy was decomposed into nonpolar, electrostatic and entropic contributions. A free energy–surface area relationship served to calculate the nonpolar free energy term. The electrostatic free energy was calculated with the finite difference Poisson‐Boltzmann method and the entropic contribution was estimated from the loss in the conformational entropy of the peptide side chains.

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