BiHiTo: Biomolecular Hierarchy-inspired Tokenization

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Authors: Association for Artificial Intelligence 2026, Jie Chen, Xuehan Hou, Yutian Liu, Chang Liu, Siwei Ma, Youdong Jack Mao, Zhiwei Nie, Yian Zhao, Ruochong Zheng
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Abstract

Three-dimensional atomic arrangements of biomolecules are key to demystifying biological functions. The rapid expansion of accessible structural data, driven by advances in AI for science, highlights the critical challenge of efficiently modeling large-scale biomolecular structures, which are high-dimensional systems shaped by biological assembly principles. To address this, we introduce BiHiTo, a multi-level Biomolecular Hierarchy-inspired Tokenizer that intrinsically mimics natural biological assembly hierarchies. Specifically, we design a multi-codebook quantizer that mirrors the natural hierarchy of biomolecular structure, enabling simultaneous capture of representations spanning atomic motifs to global conformational variations. This hierarchical alignment markedly improves the biological interpretability and reconstruction fidelity of biomolecular structure.Extensive experiments demonstrate that BiHiTo delivers state-of-the-art performance and robust generalization across molecular dynamics trajectories and macromolecular complexes, facilitating advances in structure generation and dynamic conformation exploration. In the reconstruction of the CASP14 and OOD test set FastFolding protein multi-conformation data, our method achieves a 17% and 51% reduction in RMSD compared to Bio2Token, respectively.

Fields of Study & Subjects

Protein Structure and Dynamics Computational Drug Discovery Methods Machine Learning in Bioinformatics

Publication details

Journal / source
Underline Science Inc.
Publication date
7 January 2026
Language
EN