{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/out-of-many-one-designing-and-scaffolding","title":"Out of Many, One: Designing and Scaffolding Proteins at the Scale of the Structural Universe with Genie 2","arxiv_id":"2405.15489","date":"2024-05-24","proceeding":null,"authors":["Yeqing Lin","Minji Lee","Zhao Zhang","Mohammed AlQuraishi"],"abstract":"Protein diffusion models have emerged as a promising approach for protein design. One such pioneering model is Genie, a method that asymmetrically represents protein structures during the forward and backward processes, using simple Gaussian noising for the former and expressive SE(3)-equivariant attention for the latter. In this work we introduce Genie 2, extending Genie to capture a larger and more diverse protein structure space through architectural innovations and massive data augmentation. Genie 2 adds motif scaffolding capabilities via a novel multi-motif framework that designs co-occurring motifs with unspecified inter-motif positions and orientations. This makes possible complex protein designs that engage multiple interaction partners and perform multiple functions. On both unconditional and conditional generation, Genie 2 achieves state-of-the-art performance, outperforming all known methods on key design metrics including designability, diversity, and novelty. Genie 2 also solves more motif scaffolding problems than other methods and does so with more unique and varied solutions. Taken together, these advances set a new standard for structure-based protein design. Genie 2 inference and training code, as well as model weights, are freely available at: https://github.com/aqlaboratory/genie2.","url_abs":"https://arxiv.org/abs/2405.15489v1","url_pdf":"https://arxiv.org/pdf/2405.15489v1.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"out-of-many-one-designing-and-scaffolding","repo_url":"https://github.com/aqlaboratory/genie2","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":1,"framework":"pytorch","reach":null}],"tasks":[{"task_slug":"data-augmentation","task_name":"Data Augmentation"},{"task_slug":"diversity","task_name":"Diversity"},{"task_slug":"protein-design","task_name":"Protein Design"}],"methods":[{"method_slug":"diffusion","method_name":"Diffusion"},{"method_slug":"set","method_name":"SET"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"syntology_url":"https://syntology.ai/paper/2405.15489","atlas_url":"https://app.syntology.ai/?focus=2405.15489","mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}