A consistent experimental and modeling approach to light scattering studies of protein-protein interactions in solution

¹ Los Alamos National Laboratory
² Johns Hopkins University
³ University of Delaware

^* To whom correspondence should be addressed. E-mail: michaelp{at}jhu.edu.

Submitted on December 30, 2004
Revised on February 1, 2005
Accepted on 16 March 2005

	Abstract

The osmotic second virial coefficient, B₂, obtained by light scattering from protein solutions has two principal components: the Donnan contribution and a contribution due to protein-protein interactions in the limit of infinite dilution. The Donnan contribution accounts for electroneutrality in a multicomponent solution of (poly)electrolytes. The importance of distinguishing this ideal contribution to B₂ is emphasized, thereby allowing us to model the interaction part of B₂ by molecular computations. The model for protein-protein interactions that we use here extends earlier work (Neal et al., 1998) by accounting for long-range electrostatic interactions and the specific hydration of the protein by strongly associated water molecules. Our model predictions are compared with measurements of B₂ for lysozyme at 25°C over pH from 5.0 to 9.0 and 7 to 60 mM ionic strength. We find that B₂ is positive at all solution conditions and decreases with increasing ionic strength, as expected, while the interaction part of B₂ is negative at all conditions and becomes progressively less negative with increasing ionic strength. Although long-range electrostatic interactions dominate this contribution, particularly at low ionic strength, short-range electrostatic/dispersion interactions with specific hydration are essential for an accurate description of B₂ derived from experiment.

Key Words: hyrdation, light scattering, osmotic second virial coefficient, protein solution thermodynamics, protein-protein interactions, quasichemical theory

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