Discipline: Chemistry and Chemical Sciences
Subcategory: Biochemistry (not Cell and Molecular Biology and Genetics)
Achombom (Jude) Tunyi - University of Washington
Co-Author(s): Jim Pfaendtner, University of Washington, Seattle, WA
Diabetes affects about 10% of the US population and is the 7th leading cause of death. Diabetes results from either a lack of insulin production (Type 1) or resistance to it (Type 2). The active form of insulin is a 51 amino acid monomer which regulates homeostasis of blood-glucose levels. It is crucial for insulin to be structurally sound and not degraded, especially for people using insulin pumps. However, insulin has a shelf life of about 28 days unopened and only 14 days after opening the container. Efforts to improve the stability of insulin may facilitate the development of implantable pump technologies for insulin delivery and allow for longer storage of insulin. Based on a review of the literature, I hypothesize that solvation in an Ionic Liquid solution will decrease the degradation and increase the shelf-life of insulin.
To better understand the stability of the insulin protein, I compared its activity at an air-water interface to an air-ionic liquid interface. The approach consists of modeling the structure of insulin in a liquid-protein interface and using simulation software, GROMACS and PLUMED to determine its stability. Simulations of insulin were performed under specified environmentally controlled parameters for temperature, pressure and potential energy. Ten nanosecond trials in different air-liquid interfaces were then analyzed to optimize the best insulin backbone stability. The goal is to extrapolate an ammonium or imidazolium based ionic liquid solution that will decrease the aggregation of the insulin monomers. Compared to the bulk insulin form, we found that the ionic liquid-protein solution demonstrates a lower radius of gyration and a root-mean-square deviation value that levels out towards 1 Angstrom representing a stable protein. These results are also supported by a decreased hydrodynamic radius and an increased free energy of unfolding the insulin protein. These findings suggest that insulin adopts a more stable configuration and experiences decreased degradation rates in an ionic liquid solution.
The next step would be for researchers to test these computational predictions experimentally. Confirming the results would suggest that insulin in an ionic liquid solution will last longer in vitro than in a water-based solution.
Funder Acknowledgement(s): NSF REU Grant #62-4001, #62-6316 and UW LSAMP.
Faculty Advisor: Jim Pfaendtner,