Patent ID: 7065452
Filing Date: 2006-06-20
Classification: C07K,C12N

Abstract:
1. A method of using a computer for selecting at least one of a plurality of chemical entities based on its ability to associate with all or part of a molecule or molecular complex comprising a calcineurin A (CnA) binding pocket defined by structure coordinates of CnA amino acids 90, 91, 92, 118, 120, 121, 122, 150, 151, 156, 160, 199, 232, 253, 254, 256, 281, 282, 283, 284, 306, 311, 312, and 317 according to FIG. 1 ; wherein said computer comprises a machine-readable data storage medium comprising a data storage material encoded with said structure coordinates and wherein said method comprises the steps of: a) producing a crystal of a molecular complex comprising amino acids 17–392 of CnA and amino acids 1–169 of CnB; intact FKBP12; and FK506; b) determining the three-dimensional structure coordinates of the molecular complex by X-ray diffraction of the crystal; c) identifying the structural coordinates of a CnA binding pocket of said molecular complex of CnA amino acids 90, 91, 92, 118, 120, 121, 122, 150, 151, 156, 160, 199, 232, 253, 254, 256, 281, 282, 283, 284, 306, 311, 312, and 317, which coordinates fall within the range of those recited in FIG. d) utilizing said structure coordinates defining said CnA binding pocket and the structure coordinates of one of said plurality of chemical entities to position a chemical entity within all or part of the CnA binding pocket; e) docking said chemical entity with all or part of the CnA binding pocket by employing computational means which utilize said structure coordinates defining said CnA binding pocket and the chemical entity, wherein said docking utilizes energy minimization; f) analyzing the results of said docking to quantify the association between said chemical entity and all or part of the CnA binding pocket; g) optionally repeating steps d) through f) with another of said plurality of chemical entities; and h) selecting at least one of said plurality of chemical entities that associates with all or part of the CnA binding pocket based on said quantified association of said chemical entity.