用大模型提升生物分子模拟精度与规模,突破传统方法的性能瓶颈。
UBio-MolFM: A Universal Molecular Foundation Model for Bio-Systems
- 构建多保真度生物分子数据集,覆盖上千原子系统。
- 实现高达4倍的推理速度提升,支持大规模分子模拟。
- 适合计算生物学、药物设计等领域的研究人员使用。
全原子分子模拟作为理解生命机制的“计算显微镜”,受限于量子力学精度与生物尺度之间的权衡。本文提出UBio-MolFM通用基础模型框架,通过三项协同创新:(1) 构建大型生物特异性数据集UBio-Mol26,采用自下而上枚举与自上而下采样相结合的双轨策略,涵盖最多1,200原子的天然蛋白环境;(2) 提出线性扩展的等变变换器E2Former-V2,融合轴对齐稀疏化(EAAS)与长短程建模(LSR),在大系统基准测试中推理吞吐量提升约4倍;(3) 设计三阶段课程学习协议,从能量初始化过渡到能量-力一致性,以力监督缓解能量偏移。在微观力与宏观可观测物(如液态水结构、离子溶剂化、肽折叠)上的严格评测表明,UBio-MolFM在最大约1,500原子的大规模分布外生物分子系统上达到接近从头算的保真度,并生成真实分子动力学可观测结果。该模型实现了可扩展性与量子精度的统一,为下一代计算生物学提供可靠、即插即用的工具。
原文摘要 · Abstract (English)
All-atom molecular simulation serves as a quintessential ``computational microscope'' for understanding the machinery of life, yet it remains fundamentally limited by the trade-off between quantum-mechanical (QM) accuracy and biological scale. We present UBio-MolFM, a universal foundation model framework specifically engineered to bridge this gap. UBio-MolFM introduces three synergistic innovations: (1) UBio-Mol26, a large bio-specific dataset constructed via a multi-fidelity ``Two-Pronged Strategy'' that combines systematic bottom-up enumeration with top-down sampling of native protein environments (up to 1,200 atoms); (2) E2Former-V2, a linear-scaling equivariant transformer that integrates Equivariant Axis-Aligned Sparsification (EAAS) and Long-Short Range (LSR) modeling to capture non-local physics with up to ~4x higher inference throughput in our large-system benchmarks; and (3) a Three-Stage Curriculum Learning protocol that transitions from energy initialization to energy-force consistency, with force-focused supervision to mitigate energy offsets. Rigorous benchmarking across microscopic forces and macroscopic observables -- including liquid water structure, ionic solvation, and peptide folding -- demonstrates that UBio-MolFM achieves ab initio-level fidelity on large, out-of-distribution biomolecular systems (up to ~1,500 atoms) and realistic MD observables. By reconciling scalability with quantum precision, UBio-MolFM provides a robust, ready-to-use tool for the next generation of computational biology.
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