Evidence map›Paper›PMID 39934638›Full record

ArticleNature communications2025

Integrating protein language models and automatic biofoundry for enhanced protein evolution.

Qiang Zhang, Wanyi Chen, Ming Qin, Yuhao Wang, Zhongji Pu, Keyan Ding, Yuyue Liu, Qunfeng Zhang, Dongfang Li, Xinjia Li and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Protein foundation models: a comprehensive survey.Science China. Life sciences · 2026
    Review
  12. Review
  13. Article
  14. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  15. Review
  16. Article
  17. Review
  18. AI-Driven De Novo Binder Design: From Structure Prediction to Closed-Loop Optimization.Computational and structural biotechnology journal · 2026
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Qiang Zhang *Zhejiang University, Hangzhou, Zhejiang, 310058, China.ORCID http://orcid.org/0000-0003-1636-5269
Wanyi Chen *Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Ming Qin *Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Yuhao WangZhejiang University, Hangzhou, Zhejiang, 310058, China.ORCID http://orcid.org/0009-0000-0013-7259
Zhongji PuXianghu Laboratory, Hangzhou, 311231, China.
Keyan DingZJU-Hangzhou Global Scientific and Technological Innovation Centre, Hangzhou, Zhejiang, 311200, China.ORCID http://orcid.org/0000-0003-2900-7313
Yuyue LiuZJU-Hangzhou Global Scientific and Technological Innovation Centre, Hangzhou, Zhejiang, 311200, China.
Qunfeng ZhangZhejiang University, Hangzhou, Zhejiang, 310058, China.
Dongfang LiZJU-Hangzhou Global Scientific and Technological Innovation Centre, Hangzhou, Zhejiang, 311200, China.
Xinjia LiXianghu Laboratory, Hangzhou, 311231, China.
Yu ZhaoAI Lab, Tencent, Shenzhen, Guangdong, 518000, China.ORCID http://orcid.org/0000-0001-8179-4903
Jianhua YaoAI Lab, Tencent, Shenzhen, Guangdong, 518000, China.ORCID http://orcid.org/0000-0001-9157-9596
Lei HuangZhejiang University, Hangzhou, Zhejiang, 310058, China.
Jianping WuZhejiang University, Hangzhou, Zhejiang, 310058, China.ORCID http://orcid.org/0000-0002-9924-7307
Lirong YangZhejiang University, Hangzhou, Zhejiang, 310058, China.ORCID http://orcid.org/0000-0002-6378-8451
Huajun ChenZhejiang University, Hangzhou, Zhejiang, 310058, China. huajunsir@zju.edu.cn.ORCID http://orcid.org/0000-0001-5496-7442
Haoran YuZhejiang University, Hangzhou, Zhejiang, 310058, China. yuhaoran@zju.edu.cn.ORCID http://orcid.org/0000-0001-9012-4688

Funding

National Natural Science Foundation of China (National Science Foundation of China) 22108245
6 · The paper itself

Abstract

Traditional protein engineering methods, such as directed evolution, while effective, are often slow and labor-intensive. Advances in machine learning and automated biofoundry present new opportunities for optimizing these processes. This study devises a protein language model-enabled automatic evolution platform, a closed-loop system for automated protein engineering within the Design-Build-Test-Learn cycle. The protein language model ESM-2 makes zero-shot prediction of 96 variants to initiate the cycle. The biofoundry constructs and evaluates these variants, and feeds the results back to a multi-layer perceptron to train a fitness predictor, which then makes prediction of second round of 96 variants with improved fitness. With the tRNA synthetase as a model enzyme, four-rounds of evolution carried out within 10 days lead to mutants with enzyme activity improved by up to 2.4-fold. Our system significantly enhances the speed and accuracy of protein evolution, driving faster advancements in protein engineering for industrial applications.

Indexed as

Directed Molecular EvolutionProtein EngineeringProteinsAmino Acyl-tRNA SynthetasesMachine LearningMutationAmino Acyl-tRNA SynthetasesProteins

Identifiers

PMID39934638
PMCPMC11814318

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.