Project Grant R15GM164971

Federal Grant Award Summary

Brigham Young University received a $558,383 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) for the period of July 1, 2026 through June 30, 2029. The project, "Optimization of Therapeutic Protein Pegylation by Integrating Coarse-Grain Simulation and Cell-Free Protein Synthesis," focuses on improving the efficacy of polyethylene glycol (PEG) attachment to therapeutic proteins—a critical modification that enhances pharmacokinetic stability and reduces immunogenic responses. Currently, only 3% of FDA-approved therapeutic proteins are pegylated due to limitations in control and functionality disruption caused by conventional attachment methods.

The research deliverables integrate computational modeling with laboratory validation to address this constraint. The project will employ state-of-the-art coarse-grain molecular simulations to predict optimal amino acid targeting sites for PEG attachment on therapeutic proteins, combined with rapid cell-free protein synthesis and site-specific functionalization techniques. Preliminary results have demonstrated that this simulation approach can accurately predict PEG attachment sites among hundreds of amino acids in a protein, potentially enabling broader application of pegylation in therapeutic development and substantially expanding the therapeutic benefit of this modification strategy.