{
  "abstract": "The design of novel protein sequences with targeted functionalities underpins a central theme in protein engineering, impacting diverse fields such as drug discovery and enzymatic engineering. However, navigating this vast combinatorial search space remains a severe challenge due to time and financial constraints. This scenario is rapidly evolving as the transformative advancements in AI have been propelling the protein design field into a new era. In this survey, we systematically review recent advances in generative AI for controllable protein sequence design. To set the stage, we first outline the foundational tasks in protein sequence design in terms of the constraints involved and present key generative models and optimization algorithms. We then offer in-depth reviews of each design task and discuss the in silico evaluation approaches and pertinent applications. Finally, we identify the unresolved challenges and highlight research opportunities that merit deeper exploration.",
  "abstract_shown": true,
  "affiliations": [
    "Zhongguancun Academy, Beijing, China",
    "Zhejiang University, College of Computer Science and Technology, Hangzhou, China",
    "State Key Laboratory of Transvascular Implantation Devices and TIDRI, Hangzhou, China. wujian2000@zju.edu.cn",
    "Zhejiang Key Laboratory of Medical Imaging Artificial Intelligence, Hangzhou, China. wujian2000@zju.edu.cn",
    "Zhejiang University School of Medicine, The Second Affiliated Hospital and Liangzhu Laboratory, Hangzhou, China. wujian2000@zju.edu.cn",
    "Zhejiang University, College of Pharmaceutical Sciences, Hangzhou, China",
    "Zhejiang University, Polytechnic Institute, Hangzhou, China",
    "Zhejiang University School of Medicine, The Second Affiliated Hospital and Liangzhu Laboratory, Hangzhou, China",
    "Zhejiang Provincial Key Laboratory for Intelligent Drug Discovery and Development, Jinhua, China. kimhsieh@zju.edu.cn",
    "Zhejiang University, College of Pharmaceutical Sciences, Hangzhou, China. kimhsieh@zju.edu.cn",
    "Zhejiang Provincial Key Laboratory for Intelligent Drug Discovery and Development, Jinhua, China. tingjunhou@zju.edu.cn",
    "Zhejiang University, College of Pharmaceutical Sciences, Hangzhou, China. tingjunhou@zju.edu.cn"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yiheng Zhu",
      "orcid": "0000-0002-3857-1533"
    },
    {
      "affs": [
        1
      ],
      "name": "Zitai Kong",
      "orcid": "0009-0006-1562-3288"
    },
    {
      "affs": [
        2,
        3,
        4,
        5
      ],
      "name": "Jialu Wu",
      "orcid": "0000-0003-4468-956X"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingze Yin"
    },
    {
      "affs": [
        6
      ],
      "name": "Weize Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuqiang Han"
    },
    {
      "affs": [
        7
      ],
      "name": "Hongxia Xu",
      "orcid": "0009-0003-9933-3998"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Chang‐Yu Hsieh",
      "orcid": "0000-0002-6242-4218"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Tingjun Hou",
      "orcid": "0000-0001-7227-2580"
    },
    {
      "affs": [
        2,
        3,
        4,
        5
      ],
      "name": "Jian Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wq18p7m02y8r.bib",
  "cited_by": 14,
  "doi": "10.1038/s44386-026-00054-5",
  "fulltext_url": null,
  "id": "3wq18p7m02y8r",
  "issns": [
    "3005-1452"
  ],
  "landing_url": "https://doi.org/10.1038/s44386-026-00054-5",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W4391940875",
  "pdf_url": "https://www.nature.com/articles/s44386-026-00054-5.pdf",
  "pmcid": "PMC13332047",
  "pmid": "42399444",
  "published": "2026-07-03",
  "publisher": "News UK",
  "ris": "https://research.draconitic.com/paper/3wq18p7m02y8r.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W4391940875",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s44386-026-00054-5"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Generative AI for controllable protein sequence design: A survey",
  "title_text": "Generative AI for controllable protein sequence design: A survey",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/3wq18p7m02y8r",
  "venue": "npj Drug Discovery.",
  "versions": []
}