(605d) Designing Nanotherapeutics Via Prediction of Nanoparticle-Protein Binding Interactions

Jeng, E. S., Massachusetts Institute of Technology
Strano, M. S., Massachusetts Institute of Technology

While many biological processes can be controlled by small molecule inhibitors in the binding site of a specific protein, control of most biological processes requires disruption of protein-protein interactions. Nanoparticles provide a scaffold that allows for the design of specific functional groups on a surface for binding to a larger protein-protein interfacial site. Nanoparticles can also be further functionalized with reporter molecules for tracking and sensor purposes. Although many different nanoparticle materials have been functionalized and subsequent binding with proteins has been measured experimentally, these binding events have not been modeled to date. We present a model to predict binding energies of functionalized nanoparticles with biomolecules. A standalone nanoparticle functionalizer and builder were created to allow for binding calculations between target proteins and moieties of various charges, sizes, and configurations. This model can inform about potential candidates for binding systems or reject structures to direct subsequent synthesis of the nanoparticles.