Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape
Summary: Three-dimensional structure and dynamics are essential for protein function. Advancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pha...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223003590 |
| _version_ | 1827991037772038144 |
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| author | Jiali Yu Ugur Uzuner Bin Long Zachary Wang Joshua S. Yuan Susie Y. Dai |
| author_facet | Jiali Yu Ugur Uzuner Bin Long Zachary Wang Joshua S. Yuan Susie Y. Dai |
| author_sort | Jiali Yu |
| collection | DOAJ |
| description | Summary: Three-dimensional structure and dynamics are essential for protein function. Advancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pharmaceutical industries. However, it is challenging to obtain dynamics information at the single amino acid resolution and time consuming to perform the experiments and process the data. Here, we demonstrate the first deep learning model, artificial intelligence-based HDX (AI-HDX), that predicts intrinsic protein dynamics based on the protein sequence. It uncovers the protein structural dynamics by combining deep learning, experimental HDX, sequence alignment, and protein structure prediction. AI-HDX can be broadly applied to drug discovery, protein engineering, and biomedical studies. As a demonstration, we elucidated receptor-binding domain structural dynamics as a potential mechanism of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody efficacy and immune escape. AI-HDX fundamentally differs from the current AI tools for protein analysis and may transform protein design for various applications. |
| first_indexed | 2024-04-10T00:44:27Z |
| format | Article |
| id | doaj.art-decd65adc7e04abe8503d21e89b9dfff |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T00:44:27Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-decd65adc7e04abe8503d21e89b9dfff2023-03-14T04:08:51ZengElsevieriScience2589-00422023-04-01264106282Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escapeJiali Yu0Ugur Uzuner1Bin Long2Zachary Wang3Joshua S. Yuan4Susie Y. Dai5Synthetic and Systems Biology Innovation Hub, Texas A&M University, College Station, TX 77843, USA; Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX 77843, USASynthetic and Systems Biology Innovation Hub, Texas A&M University, College Station, TX 77843, USA; Department of Molecular Biology and Genetics, Karadeniz Technical University, Trabzon 61080, TurkeySynthetic and Systems Biology Innovation Hub, Texas A&M University, College Station, TX 77843, USA; Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX 77843, USASynthetic and Systems Biology Innovation Hub, Texas A&M University, College Station, TX 77843, USADepartment of Energy, Chemical and Environmental Engineering, Washington University at St Louis, St Louis, MO 63112, USASynthetic and Systems Biology Innovation Hub, Texas A&M University, College Station, TX 77843, USA; Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX 77843, USA; Corresponding authorSummary: Three-dimensional structure and dynamics are essential for protein function. Advancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pharmaceutical industries. However, it is challenging to obtain dynamics information at the single amino acid resolution and time consuming to perform the experiments and process the data. Here, we demonstrate the first deep learning model, artificial intelligence-based HDX (AI-HDX), that predicts intrinsic protein dynamics based on the protein sequence. It uncovers the protein structural dynamics by combining deep learning, experimental HDX, sequence alignment, and protein structure prediction. AI-HDX can be broadly applied to drug discovery, protein engineering, and biomedical studies. As a demonstration, we elucidated receptor-binding domain structural dynamics as a potential mechanism of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody efficacy and immune escape. AI-HDX fundamentally differs from the current AI tools for protein analysis and may transform protein design for various applications.http://www.sciencedirect.com/science/article/pii/S2589004223003590ImmunologyVirology |
| spellingShingle | Jiali Yu Ugur Uzuner Bin Long Zachary Wang Joshua S. Yuan Susie Y. Dai Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape iScience Immunology Virology |
| title | Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape |
| title_full | Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape |
| title_fullStr | Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape |
| title_full_unstemmed | Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape |
| title_short | Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape |
| title_sort | artificial intelligence based hdx ai hdx prediction reveals fundamental characteristics to protein dynamics mechanisms on sars cov 2 immune escape |
| topic | Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223003590 |
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