Related Experiment Video
Updated: Jul 6, 2025
06:50
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
1.9K
A computational procedure for predicting excipient effects on protein-protein affinities
Gregory L Dignon1,2, Ken A Dill1,3,4
1Laufer Center for Physical and Quantitative Biology, Stony Brook University.
Biorxiv : the Preprint Server for Biology
|January 8, 2024
Summary
This study presents a computational model to predict how excipients reduce protein solution viscosity. The model successfully ranks common excipients, aiding in the development of stable biologic drugs.
Area of Science:
- Biochemistry and Pharmaceutical Sciences
- Computational Chemistry and Molecular Modeling
Background:
- Protein-protein interactions are central to biological processes and pose challenges in formulating biologic drugs like antibodies.
- Excipients, or small molecule additives, are crucial for mitigating undesirable protein association and improving drug formulation stability.
Approach:
- Developed a computationally efficient model integrating molecular dynamics (MD) simulations, binding polynomials, and thermodynamic perturbation theory.
- Utilized atomic-resolution MD simulations to capture molecular interactions and predict thermodynamic properties.
Key Points:
- The model successfully predicts and rank orders the viscosity-reducing effects of four common excipients for a specific monoclonal antibody solution.
- Demonstrated the model's utility in assessing excipient impact on protein association and phase separation.
Conclusions:
- The developed computational approach offers a valuable tool for predicting excipient efficacy in protein formulations.
- This method can guide the selection of optimal excipients and buffers to enhance the stability and manufacturability of protein-based therapeutics.
Related Concept Videos
02:04Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
01:22Protein-Drug Binding: Determination Methods
194
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
194
02:18The Equilibrium Binding Constant and Binding Strength
12.9K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
12.9K
02:26Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
45
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
45