NIST · Open Source · NIST AI
Flexible Protein Simulations of Monoclonal Antibodies to Enable Biotherapeutic Development
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★ Tier-1 Source
All-atom modeling and dynamics refines design of protein therapeutics by incorporating dynamics in low and high concentration formulations.
Key facts
- Classifying Biomolecular Structures through Unsupervised Learning Techniques” Spring ACS, CINF Section March 2024
- Incorporating Dynamics to Advance Biotherapeutic Platform Development” LINXS Webinar June 2023
- Building Computational Models to Advance Biotherapeutic Platform Development” NIST Biophysical and Biomedical Measurements Group Meeting February 2023
- Incorporating Dynamics to Advance Biotherapeutic Platform Development” Virginia Tech Biochemistry March 2023
Summary
In several projects, computational work integrates with experimental work to tell them something about the critical quality attributes of this highly flexible molecule. Grow from the “static sphere” model to interpret experiments. Formulating them at high concentrations is difficult because they tend to cluster and aggregate, which raises viscosity and shortens shelf‑life. Because the hinge is highly flexible and largely unstructured, conventional structural experiments (cryo‑EM, X‑ray crystallography) provide little insight. Additionally, they have determined a method for free energy readout in the Fc domain, a target for modulating effector functions in vivo. Kleczynski, M., Bergonzo, C.*, Kearsley, A.J. Spatial and sequential topological analysis of molecular dynamics simulations of IgG1 Fc domains. Szalai, V., Bergonzo, C.*, Lyon, R., Kelman, Z., Schmidt, T., Grishaev, A.