INSIGHTS INTO FAST DYNAMICS DETERMINING PROTEIN PRESERVATION IN SUGAR GLASSES

 

David S. Simmons, Jack Douglas

 

Encapsulation in sugar-based glasses has long been employed to stabilize proteins against low temperatures and dehydration.  However, the molecular origins of this effect have been unclear, and it fails to adequately preserve over one-third of protein based drugs.  Recent experimental results have indicated that preservation time is strongly correlated with short-time dynamics of the glass.  We employ molecular dynamics simulations to investigate interrelations between several measures of fast dynamics in glasses in order to elucidate the precise molecular origin of their preservative effect.  Results show that several of these measures are interrelated through the Gaussian approximation, which treats the distribution of particle displacements as being Brownian in nature.  They also demonstrate the presence of a post-inertial process that exhibits signs of being cooperative in nature.  Evidence suggests that the tuning of this process may be a central effect in formulations designed to improve preservation.