REPROGRAMMING EFFECTIVE PROTEIN INTERACTIONS TO CORRECT EPIGENETIC DEFECTS IN A MALIGNANT TUMOR

摘要

1. A method for identifying candidate compounds that modulate the binding of histone tag reading protein to a histone tail, comprising: (a) calculating a structural model of a reading protein active site in combination with a histone tail tag target, a structural model based on a computational model of active the site of the reading protein in combination with its related histone tail tag; (b) identification of one or more functional features necessary for binding to the target histone tag th tail in the active site of the protein reading; and (c) screening candidate compounds to identify those that, together with the residues in the active site and the target tag of the histone tail, substantially reproduce the functional features identified in stage (b) .2. The method of claim 1, wherein step (c) further includes obtaining a probe structure using a structural model that, together with the residues in the active site and the target tag of the histone tail, essentially reproduces the functional features defined in step (b), and screening candidate compounds based on probe structure and structural model. 3. The method of claim 2, wherein obtaining the probe structure includes iterative modeling of the molecular dynamics of a series of probe structures in the active site with a histone tail tag target to identify the optimal probe structure that provides a stable complex between the probe structure, residues in the active site and the target histone tail mark. 4. The method of claim 3, wherein screening the candidate compounds includes docking the compound