The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolecules. Here we review the status of KB theory as applied to biological systems. In particular, the existing models of denaturation are analyzed in terms of KB theory, and the use of KB theory to interpret computer simulation data for these systems is discussed.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566781 | PMC |
http://dx.doi.org/10.1007/s12013-007-9005-0 | DOI Listing |
J Phys Chem B
October 2024
Boehringer Ingelheim Pharma GmbH & Co. KG, Development NCE, Biberach D-88397, Germany.
We study the influence of urea on the stability of monoclonal antibodies (mAbs) using molecular dynamics (MD) simulations in combination with differential scanning fluorimetry (DSF). We show that a denaturing cosolute such as urea binds strongly to the protein, which can lead to denaturation and enhanced aggregation behavior at high temperatures. The interaction between protein and urea crucially depends on the surface properties of the individual mAb domains and therefore affects the general binding to the protein differently.
View Article and Find Full Text PDFJ Phys Chem B
June 2024
Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
Mixing two solvents can sometimes make a much better solvent than expected from their weighted mean. This phenomenon, called synergistic solvation, has commonly been explained via the Hildebrand and Hansen solubility parameters, yet their inability in other solubilization phenomena, most notably hydrotropy, necessitates an alternative route to elucidating solubilization. While, recently, the universal theory of solubilization was founded on the statistical thermodynamic fluctuation theory (as a generalization of the Kirkwood-Buff theory), its demand for experimental data processing has been a hindrance for its wider application.
View Article and Find Full Text PDFJ Phys Chem B
May 2024
School of Transdisciplinary Innovations, Seoul National University, Seoul 08826, Republic of Korea.
Surfactant-free microemulsion (SFME) represents a class of fluid mixtures that can form microheterogeneous structures without detergents, offering an environmentally benign alternative to traditional microemulsions. However, the formation mechanism is still elusive. This work applies the Kirkwood-Buff theory to mixtures of alcohols, water, and -hexane to elucidate the SFME formation mechanism.
View Article and Find Full Text PDFJ Chem Theory Comput
May 2024
Sorbonne Université, Laboratoire de Physique Théorique de la Matière Condensée (UMR CNRS 7600), 4 Place Jussieu, F75252 Paris cedex 05, France.
The structural properties of aqueous 1-4 dioxane mixtures are studied by computer simulations of different water and dioxane force field models, from the perspective of illustrating the link between structural properties at the molecular level and measurable properties such as radiation scattering intensities and Kirkwood-Buff integrals (KBIs). A strategy to consistently correct the KBI obtained from simulations is proposed, which allows us to obtain the genuine KBI corresponding to a given pair of molecular species, in the entire concentration range, and without necessitating excessively large system sizes. The application of this method to the aqueous dioxane mixtures, with an all-atom CHARMM dioxane model and 2 water models, namely, SPC/E and TIP3P, allows one to understand the differences in the structure of the corresponding mixtures at the molecular level, particularly concerning the role of the water aggregates and its model dependence.
View Article and Find Full Text PDFMAbs
April 2024
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) solutions, we measured the viscosities, the second virial coefficients, the Kirkwood-Buff integrals, and the cluster distributions of the antibody molecules as functions of protein concentration. Solutions were modeled using the statistical-physics Wertheim liquid-solution theory, representing antibodies as Y-shaped molecular structures of seven beads each.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!