SBIR Phase I: Nonlinear optical method for identifying protein-ligand binding sites

Award ID: 2111821

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to develop a technique that can reveal where precisely a small molecule, such as a potential drug, interacts with a protein on its surface. Proteins, particularly when mutated, are among the most frequent drivers of human disease. Drugs exert their effects by binding to the surface of a disease-causing protein and turning off the protein or otherwise changing its shape, which is critical for a proteins function, so that the disease process is ameliorated or even halted. To develop effective drugs, a key piece of information is how and where on the surface precisely a small molecule binds to its target protein. This information is often challenging to obtain using conventional techniques such as X-ray crystallography or nuclear magnetic resonance (NMR). This project will develop a technique that could be used broadly for drug discovery. This Phase I project aims to develop a technique using a nonlinear optical method to identify the binding location of a small molecule on the surface of two cancer-causing proteins. Two proteins with small molecule ligands will be used to demonstrate feasibility of the technique, for which X-ray co-structures exist, providing a means to benchmark the findings of the proposed technique. The proposed technique will be based on a nonlinear optical technique that is sensitive to protein structure and ligand-induced conformational changes. The proteins will be labeled and detected by the optical technique, enabling measurements which will be analyzed to determine a ligands binding site. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Program Director: Erik Pierstorff