System and method for high throughput screening of small molecule-protein interactions

A method for high throughput screening of small molecule-protein interactions comprising:

• selecting a tissue;
• selecting small molecules for screening;
• forming a matrix;
• binding the small molecule to a matrix using a linker resulting in immobilization of the small molecule;
• converting the tissue mRNA to cDNA;
• establishing a cDNA library;
• making a phage display library;
• mixing the phage library with the selected small molecules coupled to the matrix;
• incubating the mixture;
• washing the incubated mixture to remove unbound phage;
• amplifying the bound phage;
• biopanning using the bound phage;
• repeating biopanning;
• undertaking PCR of the individual plaques selected from the final biopanning round;
• barcoding the PCR products;
• pooling the barcoded PCR products;
• subjecting the pooled PCR products to Nextgen sequencing;
• correlating the resulting protein-small molecule interactions identified following screening with literature to identify disease pathways involved with the protein;
• and
• validating the protein-small molecule interactions.

A method for high throughput screening of small molecule-protein interactions comprising:

• selecting a tissue;
• selecting small molecules for screening;
• forming a matrix;
• immobilizing the small molecule on the matrix;
• converting the tissue mRNA to cDNA;
• establishing a cDNA library;
• making a phage display library;
• mixing the phage library with the immobilized small molecules;
• incubating the mixture;
• washing the incubated mixture to remove unbound phage;
• amplifying the bound phage;
• biopanning using the bound phage;
• repeating biopanning;
• undertaking PCR of the individual plaques selected from the final biopanning round;
• barcoding the PCR products;
• pooling the barcoded PCR products;
• and
• sequencing the pooled PCR products.