Protein Structure in Amorphous Solid Phase

Abstract

Protein-based medicines often require freezing or stabilization in carbohydrate glasses for storage prior to use. The structural stability of these proteins is of the great importance in the conditions required for pharmaceutical purposes. Problems involving aggregation and stability of the protein in freeze-dried formulations are of the challenges for the pharmaceutical industry.Small-angle neutron scattering (SANS) is uniquely qualified to study the structure of proteins in the liquid and solid phases that are biotechnologically relevant for proteins. The structural and conformational changes of a model protein, lysozyme, during the destabilizations in water- ice and carbohydrates systems were studied using SANS and MD simulations. X-ray diffraction measurements were performed to verify existence of cubic and hexagonal ice structures in protein-ice system. Measurements and modelling efforts to understand protein structural changes will be discussed and the interaction distances measured by SANS and proposed model protein structures in different carbohydrate glasses will be compared.