IMPROVING PK(A) CALCULATIONS WITH CONSIDERATION OF HYDRATION ENTROPY

Continuum dielectric modelling of electrostatics interactions in macro molecules provides a valuable tool in the study of structure-function relationships, but falls short of providing consistently accurate calc ulated pK(a)s. It is suggested that the model can be significantly imp roved with the inclusion of a term that estimates the entropy associat ed with first hydration shell solvent ordering, with reference to comp uted results for cysteines in DsbA and thioredoxin, and aspartic and g lutamic acids in a number of proteins, The modification is based on th e geometry of charge burial and an hydration number, which is adjustab le (by fit to experiment), and is uniform within each class of ionizab le group studied, The potential for further development is clear withi n this framework, since experiment and simulation can furnish non-adju stable, ionizable group-specific, hydration numbers.