Sublimation Entropy and Dissociation Constants Prediction by Quantitative Evaluation of Molecular Mobility in Crystals.

Prediction of binding free energies (or dissociation constants) is a crucial challenge for computational biochemistry. One of the main problems here consists in fast and accurate evaluation of binding entropy, which is far more time-consuming than evaluation of binding enthalpy. Here, we offer a fast and rather accurate approach to evaluate the sublimation entropy (i.e., entropy of binding of a vapor molecule to a crystal, taken with the opposite sign) from the average range of molecular movements in the solid state. To estimate this range (and the corresponding amplitude), we considered equilibrium sublimation of small organic molecules from molecular crystals. The calculations were based on experimental data on the sublimation enthalpy, pressure of saturated vapor, and structural characteristics of the molecule in question. The resulting average amplitude (0.17 ± 0.01 Å) of molecular movements in crystals was used to predict sublimation entropies and dissociation constants for sublimation of 28 molecular crystals. The results of these predictions are in close agreement with experimental values.