DEVELOPMENT OF MULTISCALE, MULTIPHYSICS SIMULATION OF PROTEIN STABILITY UNDER HYDRODYNAMIC STRESS

Monoclonal antibodies have presented a unique opportunity for drugs to be designed according to biological processes and functions. Along with this comes the unique challenge of designing stable protein therapeutics outside the bounds of their native environment. The most consequential misstep during formulation or manufacture that leads to instability is an adverse immunological effect on patients. Efforts during the formulation and manufacture of biotherapeutics therefore lie predominantly on improving stability and retaining drug efficiency, by studying pathways and environments that influence protein stability. Advancements in computational methods for studying proteins in chemical environments have informed and refined previous assumptions about some of the convoluted pathways of protein interactions and dynamics. However, the task remains daunting due to the precarious nature/structure of proteins which is also tied to their function. Through a multiscale-multiphysics modeling approach, this project seeks to expand the current understanding of modeling hydrodynamic-induced stress on protein structure/function and advance the ongoing efforts to unravel the intricate makings of proteins, especially as therapeutics. This modeling framework accounts for the macroscopic quantities that underscore destabilizing events in protein-fluid environments and describes these events at the microscopic level using mesoscopic simulations as a bridge. The refining qualities of each simulation scale provide sufficient descriptors of stress and protein dynamics at the onset of instability.