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ShanghaiTech University Knowledge Management System
A general temperature-guided language model to design proteins of enhanced stability and activity | |
Jiang, Fan1; Li, Mingchen2,3; Dong, Jiajun4,5 ![]() ![]() ![]() ![]() ![]() | |
2024-11-29 | |
发表期刊 | SCIENCE ADVANCES (IF:11.7[JCR-2023],13.7[5-Year]) |
ISSN | 2375-2548 |
EISSN | 2375-2548 |
卷号 | 10期号:48 |
发表状态 | 已发表 |
DOI | 10.1126/sciadv.adr2641 |
摘要 | Designing protein mutants with both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants with improved stability and activity without any prior experimental mutagenesis data for the specified protein. Leveraging temperature-aware language modeling, PRIME demonstrated superior predictive ability compared to current state-of-the-art models on the public mutagenesis dataset across 283 protein assays. Furthermore, we validated PRIME’s predictions on five proteins, examining the impact of the top 30 to 45 single-site mutations on various protein properties, including thermal stability, antigen-antibody binding affinity, and the ability to polymerize nonnatural nucleic acid or resilience to extreme alkaline conditions. More than 30% of PRIME-recommended mutants exhibited superior performance compared to their premutation counterparts across all proteins and desired properties. We developed an efficient and effective method based on PRIME to rapidly obtain multisite mutants with enhanced activity and stability. Hence, PRIME demonstrates broad applicability in protein engineering. © 2024 the Authors, some rights reserved; |
关键词 | Antigen-antibody reactions Antigens 'current Enhanced stability Language model Learning models Predictive abilities Property Protein engineering Protein mutants State of the art Temperature aware |
URL | 查看原文 |
收录类别 | EI ; PPRN.PPRN ; SCI |
语种 | 英语 |
资助项目 | National Natural Science Foundation of China["12104295","11974239","32471536"] ; National Key Research and Development Program of China[2021YFF1200200] ; Innovation Program of Shanghai Municipal Education Commission[2019-01-07-00-02-E00076] ; Shanghai JiaoTong University Scientific and Technological Innovation Funds[21X010200843] ; Computational Biology Key Program of Shanghai Science and Technology Commission[23JS1400600] ; Science and Technology Innovation Key R&D Program of Chongqing[CSTB2022TIAD-STX0017] |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:001402031000010 |
出版者 | American Association for the Advancement of Science |
EI入藏号 | 20245017502957 |
EI主题词 | Biochemical engineering |
EI分类号 | 103.2 ; 805.1 Chemical Engineering |
原始文献类型 | Journal article (JA) |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/461527 |
专题 | 免疫化学研究所 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 免疫化学研究所_PI研究组_刘佳组 |
通讯作者 | Song, Jie; Liu, Jia; Hong, Liang; Tan, Pan |
作者单位 | 1.School of Physics and Astronomy, & Shanghai National center for Applied Mathematics (SJtU center), & institute of Natural Sciences, Shanghai Jiao tong University, Shanghai; 200240, China; 2.Shanghai Artificial intelligence laboratory, Shanghai; 200030, China; 3.School of information Science and engineering, East china University of Science and technology, Shanghai; 200240, China; 4.Shanghai institute for Advanced immunochemical Studies, School of life Sciences and technology, Shanghaitech University, Shanghai; 201210, China; 5.Guangzhou National laboratory, Guangzhou international Bio island, No. 9 XingdaohuanBei Road, Guangdong, Guangzhou; 510005, China; 6.Department of chemistry, University of Science and technology of china, Anhui, Hefei; 230001, China; 7.hangzhou institute of Medicine, chinese Academy of Sciences, Zhejiang, Hangzhou; 310018, China; 8.School of life Sciences and Biotechnology, & State Key laboratory of Microbial Metabolism, Joint international Research laboratory of Metabolic, Shanghai Jiao tong University, Shanghai; 200240, China; 9.Sensetime Research, Shanghai; 200233, China; 10.Institute of Key Biological Raw Material, Shanghai Academy of experimental Medicine, Shanghai; 201401, China; 11.hzymes Biotechnology co. ltd, hubei, Wuhan; 430075, China; 12.Zhanjiang institute for Advanced Study, Shanghai Jiao tong University, Shanghai; 200240, China |
通讯作者单位 | 免疫化学研究所 |
推荐引用方式 GB/T 7714 | Jiang, Fan,Li, Mingchen,Dong, Jiajun,et al. A general temperature-guided language model to design proteins of enhanced stability and activity[J]. SCIENCE ADVANCES,2024,10(48). |
APA | Jiang, Fan.,Li, Mingchen.,Dong, Jiajun.,Yu, Yuanxi.,Sun, Xinyu.,...&Tan, Pan.(2024).A general temperature-guided language model to design proteins of enhanced stability and activity.SCIENCE ADVANCES,10(48). |
MLA | Jiang, Fan,et al."A general temperature-guided language model to design proteins of enhanced stability and activity".SCIENCE ADVANCES 10.48(2024). |
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