COMPUTATIONAL PROTEIN PROBING TO IDENTIFY BINDING SITES

Provided is a computer-implemented method of analyzing a macromolecule for potential binding sites that includes: positioning an instance of a computer representation of a molecule or molecular fragment at a plurality of sampling sites of the macromolecule; selecting a value of B, wherein B=&mgr;&#8242;/kT+1n<N>, where &mgr;&#8242; is the excess chemical potential, k is Boltzmann's constant, T is the absolute temperature, and <N>is the mean number of molecules of the molecule or molecular fragment; repositioning the instances of the molecule or molecular fragment; accepting or rejecting each instance of the repositioned molecule or molecular fragment based on the Metropolis sampling criteria using the computed binding energy compared to the selected value of B; repeating these steps at a lesser value of B; outputting a list of unrejected instances of the molecule or molecular fragment, wherein the molecule or molecular fragment is an organic fragment; and outputting a list of one or more clusters of sampling sites, wherein the clusters of sampling sites include closely located or superimposed sampling sites associated with the unrejected instances of the molecule or molecular fragment.