title: Investigating Structure and Dynamics of Proteins in Amorphous Phases Using Neutron Scattering.
abstract: In order to increase shelf life and minimize aggregation during storage, many biotherapeutic drugs are formulated and stored as either frozen solutions or lyophilized powders. However, characterizing amorphous solids can be challenging with the commonly available set of biophysical measurements used for proteins in liquid solutions. Therefore, some questions remain regarding the structure of the active pharmaceutical ingredient during freezing and drying of the drug product and the molecular role of excipients. Neutron scattering is a powerful technique to study structure and dynamics of a variety of systems in both solid and liquid phases. Moreover, neutron scattering experiments can generally be correlated with theory and molecular simulations to analyze experimental data. In this article, we focus on the use of neutron techniques to address problems of biotechnological interest. We describe the use of small-angle neutron scattering to study the solution structure of biological molecules and the packing arrangement in amorphous phases, that is, frozen glasses and freeze-dried protein powders. In addition, we discuss the use of neutron spectroscopy to measure the dynamics of glassy systems at different time and length scales. Overall, we expect that the present article will guide and prompt the use of neutron scattering to provide unique insights on many of the outstanding questions in biotechnology.
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 6102, Gaithersburg, MD 20899, United States; Institute for Bioscience and Biotechnology Research, 9600 Gudelsky Drive, Rockville, MD 20850, United States.
authors.forename: Maria Monica
authors.initials: MM
authors.lastname: Castellanos
authors.affiliation: Department of Drug Product Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors.forename: Arnold
authors.initials: A
authors.lastname: McAuley
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 6102, Gaithersburg, MD 20899, United States.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Curtis
keywords: Freeze-dried proteins; Frozen protein solutions; Glasses; Molecular dynamics; Neutron scattering; Protein dynamics; Protein structure