Conclusions

Different reference states in knowledge-based scoring functions lead to different predictions of binding affinities. A reference state that most comprehensively captures the effects of protein-ligand solvation consistently yields the best correlation between calculated PMF score and measured binding affinities for four different sets of protein-ligand complexes taken from the Brookhaven Protein Data Bank. The minimum radius of a reference sphere that is capable of capturing solvation effects effectively must be greater than 6 A. A reference sphere radius of at least 7-8 A is found to be sufficient to get good correlation between measured binding affinities and calculated score. A radius of 9 A is found to be optimal but not significantly better than larger radii.

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