ArticleProtein engineering, design & selection : PEDS2022
Stabilization of the SARS-CoV-2 receptor binding domain by protein core redesign and deep mutational scanning.
Article in Protein engineering, design & selection : PEDS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Graph attention with structural features improves the generalizability of identifying functional sequences at a protein interface.bioRxiv : the preprint server for biology · 2025Article
- Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV.Frontiers in immunology · 2025Article
- Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens.NPJ vaccines · 2024Article
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unraveling the Dynamics of SARS-CoV-2 Mutations: Insights from Surface Plasmon Resonance Biosensor Kinetics.Biosensors · 2024Review
- Deep mutational scanning of proteins in mammalian cells.Cell reports methods · 2023Review
- Epistasis and pleiotropy shape biophysical protein subspaces associated with drug resistance.Physical review. E · 2023Article
- Topological deep learning based deep mutational scanning.Computers in biology and medicine · 2023Article
- Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.bioRxiv : the preprint server for biology · 2023Article
- Repertoire of Computationally Designed Peroxygenases for Enantiodivergent C-H Oxyfunctionalization Reactions.Journal of the American Chemical Society · 2023Article
- Article
- Prediction of antibody binding to SARS-CoV-2 RBDs.Bioinformatics advances · 2023Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Stabilizing antigenic proteins as vaccine immunogens or diagnostic reagents is a stringent case of protein engineering and design as the exterior surface must maintain recognition by receptor(s) and antigen-specific antibodies at multiple distinct epitopes. This is a challenge, as stability enhancing mutations must be focused on the protein core, whereas successful computational stabilization algorithms typically select mutations at solvent-facing positions. In this study, we report the stabilization of SARS-CoV-2 Wuhan Hu-1 Spike receptor binding domain using a combination of deep mutational scanning and computational design, including the FuncLib algorithm. Our most successful design encodes I358F, Y365W, T430I, and I513L receptor binding domain mutations, maintains recognition by the receptor ACE2 and a panel of different anti-receptor binding domain monoclonal antibodies, is between 1 and 2°C more thermally stable than the original receptor binding domain using a thermal shift assay, and is less proteolytically sensitive to chymotrypsin and thermolysin than the original receptor binding domain. Our approach could be applied to the computational stabilization of a wide range of proteins without requiring detailed knowledge of active sites or binding epitopes. We envision that this strategy may be particularly powerful for cases when there are multiple or unknown binding sites.
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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.