ArticleMolecular pharmaceutics2022
Understanding the Stabilizing Effect of Histidine on mAb Aggregation: A Molecular Dynamics Study.
Article in Molecular pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 75 citations in OpenAlex.
- Article
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- Review
- Frozen storage of mAbs at elevated temperatures: Balancing stability and sustainability.International journal of pharmaceutics: X · 2026Article
- The colder, the better? Sustainability in frozen storage of a monoclonal antibody drug substance.International journal of pharmaceutics: X · 2026Article
- Molecular origins of opalescence and phase separation in mAb formulations and their relation to aggregation.Communications chemistry · 2026Article
- Impact of Amino Acid Excipients on icIEF Method Development in Protein Therapeutics: A Formulation-Aware Analytical Framework.AAPS PharmSciTech · 2026Article
- Modulation of Intravenous Immunoglobulin Aggregation, Subvisible Particle Formation, and Viscosity by Acetylated Amino Acids.Pharmaceutics · 2026Article
- Comparative Evaluation of Carbohydrate, Amino Acid, and Ionic Liquid Excipients for Flavivirus Vaccine Stabilization.ACS omega · 2026Article
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Emerging Technologies and Integrated Interdisciplinary Strategies for Mitigating Protein Aggregation in Therapeutic Formulations.Pharmaceutical research · 2026Review
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- Monoclonal antibody formulations: a quantitative analysis of marketed products and patents.mAbs · 2025Article
- Formulation of Recombinant Therapeutic Proteins: Technological Innovation, Regulations, and Evolution Towards Buffer-Free Formulations.Pharmaceutics · 2025Review
- Stabilising proteins in solution using affordable and readily available small molecules.Biophysical reviews · 2025Review
- Design Principles for Engineering Ionic Liquid-Gold Nanoparticles for Therapeutic Delivery to the Brain.ACS nano · 2025Article
- Protease-Catalyzed Synthesis of Water-Soluble Oligohistidine.Industrial biotechnology (New Rochelle, N.Y.) · 2025Article
- Improving the thermostability and substrate affinity of3 Biotech · 2025Article
- Effects of buffers on spray-freeze-dried/lyophilized high concentration protein formulations.International journal of pharmaceutics · 2025Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understanding this mechanism will help evaluate and predict the stabilizing effect of this buffer under different experimental conditions and for different mAbs. We have used all-atom molecular dynamics simulations and contact-based free energy calculations to investigate molecular-level interactions between the histidine buffer and mAbs, which lead to the observed stability of therapeutic formulations in the presence of histidine. We reformulate the Spatial Aggregation Propensity index by including the buffer-protein interactions. The buffer adsorption on the protein surface leads to lower exposure of the hydrophobic regions to water. Our analysis indicates that the mechanism behind the stabilizing action of histidine is connected to the shielding of the solvent-exposed hydrophobic regions on the protein surface by the buffer molecules.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.