Patent ID: 8566072
Filing Date: 2013-10-22
Classification: C07K,G01N,G16B

Abstract:
1. A method for forming a first peptide inhibitor of a CDK/cyclin D complex, the method comprising: generating an in silico model comprising a second peptide inhibitor bound to a cyclin protein, this cyclin protein differing from the cyclin D of the CDK/cyclin D complex; superimposing the cyclin D of the CDK/cyclin D complex on the in silico model such that an corresponding alpha carbon atoms of the cyclin D of the CDK/cyclin D complex and an of the cyclin protein are overlayed and the binding sites of the two cyclins are sequence aligned with one another; deleting the cyclin protein from the in silico model to form a second in silico model of the second peptide inhibitor bound to the cyclin D of the CDK/cyclin D complex, wherein the deletion is carried out in steps such that an energy minimum is converged upon; determining the location of conformation differences between the model of the cyclin protein bound to the second peptide inhibitor and the model of the cyclin D protein of the CDK/cyclin D complex bound to the second peptide inhibitor; altering the structure of the second peptide inhibitor to develop an in silico model of the first peptide inhibitor, the structure alteration comprising replacement of one or more residues of the second peptide inhibitor with a different amino acid or a synthetic substituent; and forming the first peptide inhibitor based upon the in silico model of the first peptide inhibitor, and testing whether the affinity of the cyclin D protein of the CDK/cyclin D complex to the first peptide inhibitor is greater than the affinity of the cyclin D protein of the CDK/cyclin D complex to the second peptide inhibitor.