Patent ID: 8019550

Claim:
A method of obtaining information about a chemically active area of a target molecule, comprising: (a) selecting a compound that is a substantially rigid chemical gauge comprising at least one set of three binding points in a substantially rigid triangular configuration, each of said at least one set of three binding points being selected capable of binding to a 3-point pharmacophore comprising a triplet of chemical binding points selected from the group consisting of acid, base, hydrophobic, hydrogen-bond donor, hydrogen-bond acceptor, and aromatic, wherein each pair of binding points of said 3-point pharmacophore is separated by a distance in a range of 2 to 12 angstrom; (b) performing an assay for measuring an interaction of said target molecule with said gauge, thereby obtaining an assay result for said gauge; (c) selecting additional substantially rigid chemical gauges according to said (a) so as to obtain a plurality of gauges, such that for a portion of triangle space comprising 50% of said triangle space, said plurality of gauges is selected such that for each 3-point pharmacophore corresponding to a point in said portion of triangle space, said plurality of gauges comprises at least six gauges with a substantially rigid triangular configuration of binding points capable of chemically binding to said 3-point pharmacophore, wherein said triangle space defines all possible 3-point pharmacophores defined by a triplet of distances that form a triangle, each distance being in a range of 2-12 angstrom, and by a triplet of chemical binding point types for the triangle vertices, each chemical binding point type being selected from the group consisting of acid, base, hydrophobic, hydrogen-bond donor, hydrogen-bond acceptor, and aromatic, and wherein said point in said triangle space is defined by six coordinates, three of said coordinates being for defining the three distances in said triplet of distances, and three of said coordinates being for defining the three binding point types in said triplet of chemical binding point types; (d) performing said (b) for each of said additional substantially rigid chemical gauges, so as to obtain a plurality of assay results; and (e) identifying a plurality of spatially and chemically specific configurations of binding points in said chemically active area of said target molecule using a computational model in which said assay results represent interactions between configurations of binding points in said chemically active area and triangular geometric substructures, each triangular geometric substructure representing a set of three binding points of a gauge and being defined by a triplet of distances that form a triangle and by a triplet of chemical binding point types for the triangle vertices, thereby obtaining information about said chemically active area.