Problems of Robustness in Poisson–Boltzmann Binding Free Energies

Although models based on the Poisson–Boltzmann (PB) equation have been fairly successful at predicting some experimental quantities, such as solvation free energies (ΔG), these models have not been consistently successful at predicting binding free energies (ΔΔG). Here we found that ranking a set of...

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Bibliographic Details
Published in:Journal of chemical theory and computation 2015-02, Vol.11 (2), p.705-712
Main Authors: Harris, Robert C, Mackoy, Travis, Fenley, Marcia O
Format: Article
Language:English
Subjects:
Poisson Distribution
Static Electricity
Surface Properties
Thermodynamics
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Summary:Although models based on the Poisson–Boltzmann (PB) equation have been fairly successful at predicting some experimental quantities, such as solvation free energies (ΔG), these models have not been consistently successful at predicting binding free energies (ΔΔG). Here we found that ranking a set of protein–protein complexes by the electrostatic component (ΔΔG el) of ΔΔG was more difficult than ranking the same molecules by the electrostatic component (ΔG el) of ΔG. This finding was unexpected because ΔΔG el can be calculated by combining estimates of ΔG el for the complex and its components with estimates of the ΔΔG el in vacuum. One might therefore expect that if a theory gave reliable estimates of ΔG el, then its estimates of ΔΔG el would be reliable. However, ΔΔG el for these complexes were orders of magnitude smaller than ΔG el, so although estimates of ΔG el obtained with different force fields and surface definitions were highly correlated, similar estimates of ΔΔG el were often not correlated.
ISSN:1549-9618
1549-9626
DOI:10.1021/ct5005017