Molecular Dynamics Simulation of Human Interferon β-1a PEGylated by Linear Polyethylene Glycol Polymers
PEGylation, the covalent attachment of a polyethylene glycol polymer to a molecule or protein, is known to increase the efficacy of a protein with minimal changes to immunogenic properties. The protein of interest in this study is human interferon β-1a (IFN), used in the treatment of multiple sclerosis, cancer, and viral infection. The effect of PEGylation is still poorly understood at the molecular level. In this work, we present comparative molecular dynamics simulations of Apo IFN and different mPEG-IFN conjugates in order to describe and characterize the conformational differences induced by PEGylation. The simulations allow deeper insight into the dynamics and energetics of the mPEG-IFN interactions not observable by conventional bench top experiments. A major concern of pharmaceutic development is assessing the stability of the system. We anticipate the findings of this study will have broad implications for protein pharmaceutical enhancement and development with a unique approach to the study of protein drug stability from a computational perspective.