title: Protein aggregation in salt solutions.
abstract: Protein aggregation is broadly important in diseases and in formulations of biological drugs. Here, we develop a theoretical model for reversible protein-protein aggregation in salt solutions. We treat proteins as hard spheres having square-well-energy binding sites, using Wertheim's thermodynamic perturbation theory. The necessary condition required for such modeling to be realistic is that proteins in solution during the experiment remain in their compact form. Within this limitation our model gives accurate liquid-liquid coexistence curves for lysozyme and γ IIIa-crystallin solutions in respective buffers. It provides good fits to the cloud-point curves of lysozyme in buffer-salt mixtures as a function of the type and concentration of salt. It than predicts full coexistence curves, osmotic compressibilities, and second virial coefficients under such conditions. This treatment may also be relevant to protein crystallization.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia;
authors.forename: Miha
authors.initials: M
authors.lastname: Kastelic
authors.affiliation: Institute for Condensed Matter Physics, 79011 Lviv, Ukraine;
authors.forename: Yurij V
authors.initials: YV
authors.lastname: Kalyuzhnyi
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia;
authors.forename: Barbara
authors.initials: B
authors.lastname: Hribar-Lee
authors.affiliation: Laufer Center for Physical and Quantitative Biology and Departments of Physics and Chemistry, Stony Brook University, Stony Brook, NY 11794 dill@laufercenter.org.
authors.forename: Ken A
authors.initials: KA
authors.lastname: Dill
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia;
authors.forename: Vojko
authors.initials: V
authors.lastname: Vlachy
mesh_terms: D003460:Crystallization; D008956:Models, Chemical; D009113:Muramidase / Q000737:chemistry; D009995:Osmosis; D066329:Protein Aggregates; D011506:Proteins / Q000737:chemistry*; D012492:Salts; D012996:Solutions; D049490:Systems Biology; D013816:Thermodynamics; D038222:gamma-Crystallins / Q000737:chemistry
chemical_list: D066329:Protein Aggregates; D011506:Proteins; D012492:Salts; D012996:Solutions; D038222:gamma-Crystallins; D009113:Muramidase
keywords: Hofmeister series; phase separation; protein aggregation