title: The phase behavior study of human antibody solution using multi-scale modeling.
abstract: Phase transformation in antibody solutions is of growing interest in both academia and the pharmaceutical industry. Recent experimental studies have shown that, as in near-spherical proteins, antibodies can undergo a liquid-liquid phase separation under conditions metastable with respect to crystallization. However, the phase diagram of the Y-shaped antibodies exhibits unique features that differ substantially from those of spherical proteins. Specifically, antibody solutions have an exceptionally low critical volume fraction (CVF) and a broader and more asymmetric liquid-liquid coexistence curve than those of spherical proteins. Using molecular dynamics simulation on a series of trimetric Y-shaped coarse-grained models, we investigate the phase behavior of antibody solutions and compare the results with the experimental phase diagram of human immunoglobulin G (IgG), one of the most common Y-shape typical of antibody molecules. With the fitted size of spheres, our simulation reproduces both the low CVF and the asymmetric shape of the experimental coexistence curve of IgG antibodies. The broadness of the coexistence curve can be attributed to the anisotropic nature of the inter-protein interaction. In addition, the repulsion between the inner parts of the spherical domains of IgG dramatically expands the coexistence region in the scaled phase diagram, while the hinge length has only a minor effect on the CVF and the overall shape of the coexistence curve. We thus propose a seven-site model with empirical parameters characterizing the exclusion volume and the hinge length of the IgG molecules, which provides a base for simulation studies of the phase behavior of IgG antibodies.
authors.affiliation: International Center for Quantum Materials, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Lomakin
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: George B
authors.initials: GB
authors.lastname: Benedek
authors.affiliation: Center for Polymer Studies and Department of Physics, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: H Eugene
authors.initials: HE
authors.lastname: Stanley
authors.affiliation: International Center for Quantum Materials, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Physics, Yeshiva University, 500 West 185th Street, New York, New York 10033, USA.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Buldyrev
mesh_terms: D016880:Anisotropy; D004548:Elasticity; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008958:Models, Molecular; D044367:Phase Transition; D000072417:Protein Domains
chemical_list: D007074:Immunoglobulin G