Simulated annealing of the chemical potential: A general procedure for locating bound waters. Application to the study of the differential hydration propensities of the major and minor groove of DNA.
Abstract: Grand-canonical ensemble simulations determine the distribution and density of molecules corresponding to a given chemical potential value. The method simulated annealing of chemical potential determines the solvent distribution around macromolecules at successively lower chemical potential values. This process results in a sequence of solvent distributinos, each succesive one involving fewer solvents as the one before. The last distribution will contain the solvents bound the strongest.

This method was tested on the classic DNA dodecamer of Drew & Dickerson. The result of the simulated annealing showed that, in agreement with X-ray and NMR data, the major groove empties before the minor groove. This conclusion was quantitated using proximity analysis developed in the Beveridge Laboratory.