College of Science & Engineering
These researchers are working with a 19F NMR dual screening method for detecting bromodomain-ligand interactions using fluorine-labeled aromatic amino acids on two different bromodomains. Over 200 small molecules were screened against the first bromodomain of Brd4 and the bromodomain of BPTF. Due to the absence of X-ray crystal data for the binding interactions, the Schrodinger software suite was utilized to propose probable binding poses of new small molecule binders using QM/MM hybrid techniques with Glide. These new binding classes were also analyzed to determine common pharmacophore hypotheses by Phase, in order to later develop more potent and selective inhibitors for use in drug development. The researchers are now computationally screening large libraries of drug-like compounds against various proteins to develop selective inhibitors. Additionally, they are using ab initio methods to predict chemical shifts of fluorine atoms incorporated into proteins.