Computational solvent mapping globally samples the surface of target proteins using molecular probes-small molecules or functional groups-to identify potentially favorable binding positions. The method is based on X-ray and NMR screening studies showing that the binding sites of proteins also bind a large variety of fragment-sized molecules. We have developed the multistage mapping algorithm FTMap (available as a server at http://ftmap.bu.edu/ ) based on the fast Fourier transform (FFT) correlation approach. Identifying regions of low free energy rather than individual low energy conformations, FTMap reproduces the available experimental mapping results. Applications to a variety of proteins show that the probes always cluster in important subsites of the binding site, and the amino acid residues that interact with many probes also bind the specific ligands of the protein. The "consensus" sites at which a number of different probes cluster are likely to be "druggable" sites, capable of binding drug-size ligands with high affinity. Due to its sensitivity to conformational changes, the method can also be used for comparing the binding sites in different structures of a protein.