A method for identifying a ligand binding site of a protein, the method comprising the steps of: (a) generating stochastic basis sets of values representative of putative ligand-protein binding sites by identifying information in a protein structure database, the information corresponding to known protein signature pockets and representing at least protein signature pocket atomic coordinates and conformation, and performing pair-wise sequence order-independent structure alignment, divisive hierarchical clustering, and probabilistic sequence similarity operations on the identified protein signature pocket information to select the stochastic basis sets of values representative of putative ligand-protein binding sites, the probabilistic sequence similarity operation including solution of a distance function defined by the structural similarity and likely sequence similarity of putative ligand-protein binding sites and known protein signature pockets; (b) generating basis sets of values representative of nucleotide expression levels of genes that have been correlated to known ligand-protein binding sites in a predetermined number of biological samples by mapping known ligand-protein binding site information to a gene name and identifying in a gene-biological sample expression database information representative of nucleotide expression levels corresponding to the gene; (c) selecting overlapping values from the basis sets generated in steps (a) and (b) as information which correlates to at least the atomic coordinates and conformation of one or more ligand-protein binding sites; and (d) validating the one or more ligand-protein binding sites determined in step (c) in vitro by measuring the affinity of the ligand for the one or more ligand-protein binding sites. (a) generating stochastic basis sets of values representative of putative ligand-protein binding sites by identifying information in a protein structure database, the information corresponding to known protein signature pockets and representing at least protein signature pocket atomic coordinates and conformation, and performing pair-wise sequence order-independent structure alignment, divisive hierarchical clustering, and probabilistic sequence similarity operations on the identified protein signature pocket information to select the stochastic basis sets of values representative of putative ligand-protein binding sites, the probabilistic sequence similarity operation including solution of a distance function defined by the structural similarity and likely sequence similarity of putative ligand-protein binding sites and known protein signature pockets; (b) generating basis sets of values representative of nucleotide expression levels of genes that have been correlated to known ligand-protein binding sites in a predetermined number of biological samples by mapping known ligand-protein binding site information to a gene name and identifying in a gene-biological sample expression database information representative of nucleotide expression levels corresponding to the gene; (c) selecting overlapping values from the basis sets generated in steps (a) and (b) as information which correlates to at least the atomic coordinates and conformation of one or more ligand-protein binding sites; and (d) validating the one or more ligand-protein binding sites determined in step (c) in vitro by measuring the affinity of the ligand for the one or more ligand-protein binding sites.