GLOM TGITO: multiscale protein modelling and multiview landscape-guided sequence discovery
Motivation: Offline protein design can exploit surrogate-predictor errors, favouring high-scoring sequences lacking measured support. We test whether multiscale representations and local experimental evidence improve prediction and candidate prioritization. Results: GLOM-TGITO links a global-local fluorescence predictor to multiview landscape-guided optimization. Across 31,434 measured ppluGFP2 sequences, GLOM achieved random/depth-holdout RMSEs of 0.170/0.247 versus 0.247/0.324 for the strongest SaProt-650M controls. Averaged across three training seeds, 96.3%/97.3% of prediction-ranked Top 100 test variants were measured bright (log10 fluorescence >=4.2). Search from 900 peak regions yielded 2,594 distinct candidate sequences. The selected Top 100 showed 2.9-8.2% lower mean representation deviation than four comparator pipelines; 38 versus 11-16 met joint novelty-reliability filters. Deviation identified measured test errors >0.1 (AUROC
Authors
- Shuguang Yuan (ORCID: https://orcid.org/0000-0001-9858-4742)
- Shiyu Wang (ORCID: https://orcid.org/0000-0002-8201-8022)
- Yuchen Xiong
- Zhenquan Hu
- Yosef Kristian Tirta
- Wenjing Ma
Institutions
- Chinese University of Hong Kong (HK)
- Chinese University of Hong Kong, Shenzhen (CN)
- Xiamen University Malaysia (MY)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-27
- DOI
- https://doi.org/10.64898/2026.10.22.760886
- Primary Topic
- Protein Structure and Dynamics
- Type
- preprint