Related Experiment Video
Updated: Jun 11, 2025

Author Spotlight: Detecting Low-Abundant Host Cell Proteins in Drug Products Using Enrichment Beads and Limited Digestion
Published on: January 19, 2024
Multidomain Protein-Urea Interactions: Differences in Binding Behavior Lead to Different Destabilization Tendencies
Jiyoung Yang1,2, Oliver Burkert2, Boris Mizaikoff1
1Institute for Analytical and Bioanalytical Chemistry, University of Ulm, Ulm D-89069, Germany.
None:
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. The study of these mechanisms for proteins with multiple domains, such as mAbs, encounters significant limitations in experimental analysis methods due to their complexity. Using computational and experimental methods, we are able to separate the protein-urea interaction by domain and show that Lennard-Jones interactions are mainly responsible for significant binding effects. Our results emphasize the potential of MD simulations in combination with Kirkwood-Buff theory to study the interactions between proteins with multiple domains and cosolutes as formulation excipients for drug discovery and development.
More Related Videos
10:50Purification and Analytics of a Monoclonal Antibody from Chinese Hamster Ovary Cells Using an Automated Microbioreactor System
Published on: May 1, 2019
09:45Production of Monoclonal Antibodies Targeting Aminopeptidase N in the Porcine Intestinal Mucosal Epithelium
Published on: May 18, 2021
Related Concept Videos
Factors Affecting Protein-Drug Binding: Drug Interactions
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Drug Distribution: Plasma Protein Binding
Factors Affecting Protein-Drug Binding: Protein-Related Factors
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
Cooperative Allosteric Transitions
Factors Affecting Protein-Drug Binding: Patient-Related Factors
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Factors Affecting Protein-Drug Binding: Drug-Related Factors
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...