Computationally Guided Protein-Specific Labeling with Nanoparticles

Figure 1: Papain (Blue: Catalytic Residues, Green: Predicted Surface Site)

The Integrated Graduate Education Research and Training (IGERT) fellowship provides an excellent opportunity to combine our experimental and computational tools of chemical biology with nanotechnology, with a focus toward applications in nanomedicine. These applications include imaging, diagnostics, drug discovery and drug delivery.

We propose a new approach to the labeling of human biomarker proteins with nanoparticles. We have predicted binding sites on biomarker proteins using electrostatics methods developed by us. Small molecule ligands with high, specific affinity for these sites will be attached to the biomarkers. Linker groups on the small molecules will be coupled to nanoparticles. In order to express human biomarker proteins, we had to develop new techniques for expression in bacterial systems. Using computationally guided experimental designs, we hope to provide a fast, cost effective means for the labeling of proteins with nanoparticles using highly specific coupler ligands for biomedical research.