Investigating Structure and Dynamics of Proteins in Amorphous Phases Using Neutron Scattering

Published

December 21, 2016

Author(s)

Maria Monica Castellanos Mantilla, Joseph Curtis, Arnold McAuley

Abstract

In order to increase shelf life and minimize aggregation during storage, many biotherapeutic drugs are formulated and stored as frozen solutions or as lyophilized powders during manufacturing processes. Characterizing amorphous solids can be challenging with the commonly available set of biophysical measurements used to study protein in solution. Therefore, some questions remain about how the structure of the active pharmaceutical ingredient is affected upon freezing and drying of the drug product and the molecular role of formulations excipients to increase long-term stability. Neutron scattering is a powerful technique to study the structure and dynamics of a variety of systems in both solid and liquid phase. Moreover, neutron scattering experiments can generally be correlated with theory and molecular simulations, in order to interpret experimental data. In this review article, we focus on the use of neutron techniques on proteins commonly used in biotechnology. We discuss the use of small-angle neutron scattering to study the solution structure of biological molecules, and the packing arrangement in frozen solutions and freeze-dried protein powders. In addition, we review the use of neutron spectroscopy to measure the dynamics of glassy systems at different time and length scales. Overall, we hope that the present review will guide and prompt the use of neutron scattering techniques, in order to provide unique insights on many of the outstanding questions in biotechnology.

Citation

Computational and Structural Biotechnology Journal

Volume

15

Pub Type

Journals

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Keywords

neutron scattering, protein structure, protein dynamics, freeze-dried proteins, glasses, frozen protein solutions, molecular dynamics

Citation

, M. , , J. and McAuley, A. (2016), Investigating Structure and Dynamics of Proteins in Amorphous Phases Using Neutron Scattering, Computational and Structural Biotechnology Journal, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=921876 (Accessed May 3, 2024)