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Determining accurate folding landscape using co-evolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit co-evolutionary analysis. Nevertheless, its performance still shows strong dependence on available sequence homologs. Based on the interrogation on the cause of such dependence, we presented EvoGen, a meta generative model, to remedy the underperformance of AlphaFold2 for poor MSA targets. By prompting the model with calibrated or virtually generated homologue sequences, EvoGen helps AlphaFold2 fold accurately in low-data regime and even achieve encouraging performance with single-sequence predictions. Being able to make accurate predictions with few-shot MSA not only generalizes AlphaFold2 better for orphan sequences, but also democratizes its use for high-throughput applications. Besides, EvoGen combined with AlphaFold2 yields a probabilistic structure generation method which could explore alternative conformations of protein sequences, and the task-aware differentiable algorithm for sequence generation will benefit other related tasks including protein design.","url_abs":"https://arxiv.org/abs/2208.09652v2","url_pdf":"https://arxiv.org/pdf/2208.09652v2.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":"few-shot-learning-of-accurate-folding","repo_url":"https://github.com/mindspore-ai/mindscience/tree/master/MindSPONGE/applications/MEGAProtein","is_official":1,"mentioned_in_paper":0,"mentioned_in_github":0,"framework":"mindspore","reach":{"status":"ok","spdx":"Apache-2.0"}},{"paper_slug":"few-shot-learning-of-accurate-folding","repo_url":"https://github.com/2023-MindSpore-1/ms-code-141","is_official":0,"mentioned_in_paper":0,"mentioned_in_github":0,"framework":"mindspore","reach":null}],"tasks":[{"task_slug":"denoising","task_name":"Denoising"},{"task_slug":"few-shot-learning","task_name":"Few-Shot Learning"},{"task_slug":"protein-design","task_name":"Protein Design"},{"task_slug":"protein-structure-prediction","task_name":"Protein Structure Prediction"}],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"atlas_url":"https://app.syntology.ai/?focus=2208.09652","mcp":{"get_harvested_code_for_paper":{"arxiv_id":"2208.09652"}},"developers":"https://syntology.ai/developers","read_at":"2026-09-24T18:15:14+00:00","read_at_is":"when the build read Syntology's graph, not when any sample ran","claim":"Per-sample execution status on synthesized fixtures; not a correctness claim about the paper. 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