2023 AIChE Annual Meeting

(218c) Identifying Molecular Driving Forces for Coiled-Coil Protein-Based Hydrogel Fibrilization Using Coarse-Grained Modeling

Authors

Pak, A. J., Colorado School of Mines
Stimuli-responsive protein-based hydrogels have potential as controlled/targeted drug delivery systems (DDS) due to their biocompatibility and ease of modularity [1-3]. One example is protein Q, a derivative of the coiled-coil (CC) COMPcc protein, that assembles into a thermo-responsive hydrogel scaffold capable of holding curcumin then releasing this organic molecule via an initial burst followed by sustained release kinetics [3-4]. To engineer variants of protein Q to realize their full potential as a DDS, the molecular driving forces associated with protein Q’s fibrilization and degradation must first be better understood. It is believed that electrostatic association through so-called “sticky-ends” is the main driving force for fibrilization [5-6]. However, identified variants of protein Q do not strictly follow this trend, suggesting other interactions may be important. To identify these molecular driving forces, we used an implicit-solvent coarse-grained (CG) modeling and simulation approach. We derived bottom-up CG models from atomistic molecular dynamics (MD) simulation data to infer possible driving forces, such as those due to electrostatics, intramolecular fluctuations, or amphiphilic forces mediated by solvent. Our analysis of CGMD simulations shows that solvent-mediated forces play an important role in maintaining the stability of CC protofibrils while electrostatics promote protofibril aggregation into fibrils. The future goals of this research are to determine how mutations in Q may be directed to manipulate these molecular driving forces to modify the gelation and degradation kinetics of Q-based hydrogels for DDS applications.

Works cited:

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