(626e) Protein Interactions From Kirkwood-Buff Analysis of Light Scattering and Coarse-Grained Molecular Models

Measuring and predicting colloidal protein-protein interactions (PPI) in solution is important for applications ranging from protein phase behavior to aggregation of biopharmaceuticals [1, 2]. Protein-protein interactions are often characterized via the osmotic second viral coefficient (B22), as determined from Rayleigh light scattering (LS). However, discrepancies and confusion have arisen regarding recent interpretations of B22 from classical treatment of LS data [3], as well as questions about refinement of coarse-grained models of PPI against experimental results such as B22. Here we provide an alternative treatment of Rayleigh scattering in multi-component systems based on Kirkwood-Buff (KB) solution theory, demonstrating clearly that the correct osmotic second virial coefficient can be obtained directly from light scattering. The results are compared to a generalization of Stockmayer's approach, and applied to experimental LS data for monoclonal antibodies, alpha-chymotrypsinogen A, and gamma-D crystallin. Additionally, refinement of coarse-grained models of PPI for different proteins will be presented in the context of rational protein engineering and the relative roles of steric and non-steric interactions.

[1] Asthagiri D, Paliwal A, Abras D, Lenhoff AM, Paulaitis ME: A consistent experimental and modeling approach to light-scattering studies of protein-protein interactions in solution, Biophysical Journal, 88: 3300-3309, (2005).

[2] Weiss WF, Young TM, and Roberts CJ: Principles, Approaches, and challenges for predicting protein aggregation rates and shelf life, Journal of Pharmaceutical Sciences, 98: 1246-1277, (2009).

[3] Winzor DJ, Deszczynski M, Harding SE, Wills PR: Nonequivalence of second virial coefficients from sedimentation equilibrium and static light scattering studies of protein solutions, Biophysical Chemistry, 128: 46-55, (2007)