Prediction of drug solubility from Monte Carlo simulations.

Monte Carlo statistical mechanics simulations have been carried out for 150 organic solutes in water. Physically significant descriptors such as the solvent-accessible surface area, numbers of hydrogen bonds, and indices for cohesive interactions in solids are correlated with pharmacologically important properties including octanol/water partition coefficient (log P) and aqueous solubility (log S). The regression equation for log S only requires five descriptors to provide a correlation coefficient, r2, of 0.9 and rms error of 0.7 for the 150 solutes. The descriptors can form a basis for structural modifications to guide an analogue's properties into desired ranges.