Patent ID: 6387641
Filing Date: 2002-05-14
Classification: C12N

Abstract:
A method for evaluating the ability of a compound to associate with a molecule or molecular complex comprising a protein kinase ATP binding pocket, said method comprising the steps of:a) constructing a computer model of the said binding pocket defined by structure coordinates wherein the root mean square deviation between said structure coordinates and the structure coordinates of the P38&ggr; SEQ ID NO:1 amino acids Val33, Ala40, Val41, Ala54, Lys56, Ile87, Met109, Pro110, Phe111, Met112, Gly113, Thr114, Asp115, Lys118, Asp153, Lys155, Gly157, Asn158, Ala160, Leu170, Asp171, Gly173, and Leu174 according to FIGS. 1.1-1.98 is not more than about 1.15 Ã¥; b) selecting a compound to be evaluated by a method selected from the group consisting of (i) assembling molecular fragments into said compound, (ii) selecting a compound from a small molecule database, (iii) de novo ligand design of said compound, and (iv) modifying a known inhibitor, or a portion thereof, of a protein kinase; c) employing computational means to perform a fitting program operation between computer models of the said compound to be evaluated and said binding pocket in order to provide an energy-minimized configuration of the said compound in the binding pocket; and d) evaluating the results of said fitting operation to quantify the association between the said compound and the binding pocket model, whereby evaluating the ability of the said compound to associate with the said binding pocket.