Evidence map›Paper›PMID 41565673›Full record

ArticleNature communications2026

Protein folding stability estimation with explicit consideration of unfolded states.

Heechan Lee, Yugyeong Cho, Jeongwon Yun, Martin Steinegger, Ho Min Kim, Hahnbeom Park

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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  5. Article
  6. Multimodal diffusion for joint design of protein sequence and structure.Protein science : a publication of the Protein Society · 2025
    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

6 authors.

Heechan LeeBiomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.ORCID 0009-0009-9596-5916
Yugyeong ChoDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID 0009-0005-6876-1038
Jeongwon YunDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.ORCID 0000-0003-4801-2564
Martin SteineggerSchool of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Ho Min KimDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. hm_kim@kaist.ac.kr.ORCID 0000-0003-0029-3643
Hahnbeom ParkBiomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea. hahnbeom@kist.re.kr.ORCID 0000-0002-7129-1912

Funding

Ministry of Science and ICT and Ministry of Health & WelfareNational Research Foundation of Korea
6 · The paper itself

Abstract

Folding stability is crucial for the vast majority of proteins. Computational methods suggested to date for the absolute folding stability (ΔG) prediction, including those driven from protein structure prediction AIs, show clear limitations in reproducing quantitative experimental values. Here we present IFUM, a deep neural network that jointly estimates ΔG and the equilibrium ensemble of folded and unfolded states represented by residue-pair distance probability distributions. This joint learning considerably enhances prediction accuracy compared to learning ΔG alone. Trained on a dataset including Mega-scale small proteins, disordered proteins, and wild-type natural proteins, IFUM is robust to various protein types and can accurately predict complex mutational effects like insertions or deletions. Here, we show that IFUM effectively guides real-world design challenges, exhibiting strong correlation with experimental melting temperatures in protein engineering and outperforming AlphaFold-based metrics in de novo design selection.

Indexed as

Computational BiologyProtein FoldingProteinsNeural Networks, ComputerProtein ConformationProtein StabilityProtein UnfoldingThermodynamicsProteins

Identifiers

PMID41565673
PMCPMC12923840

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Registered trials

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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.