李翛然 (2026-03-30 23:30):
#paper Learning the All-Atom Equilibrium Distribution of Biomolecular Interactions at Scale doi:10.64898/2026.03.10.710952v1 字节跳动与Anew Therapeutics推出AnewSampling,通过跳过漫长模拟直接预测分子相互作用的平衡态构象。模型基于含1500万数据的数据库,结合AlphaFold3架构,采用LoRA与全参数微调,在多项基准测试中生成结果与分子动力学模拟无统计差异。它能高效处理CDK2激酶等复杂动态过程,甚至超越常规模拟能力,为药物设计提供动态视角。当前局限包括依赖结构模板、集中于蛋白质-配体体系及固定热力学环境。
Learning the All-Atom Equilibrium Distribution of Biomolecular Interactions at Scale
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Abstract:
Abstract Biomolecular functions are governed by dynamic conformational ensembles rather than static structures. While models like AlphaFold have revolutionized static structure prediction, accurately capturing the equilibrium distribution of all-atom biomolecular interactions remains a significant challenge due to the high computational cost of molecular dynamics (MD). We present AnewSampling, a transferable generative foundation framework designed for the high-fidelity sampling of all-atom equilibrium distributions, which is the first model to faithfully reproduce MD at the all-atom level. It uses a novel quotient-space generative framework to ensure mathematical consistency and leverages the largest self-curated database of protein-ligand trajectories to date, with over 15 million conformations. Statistically, AnewSampling consistently outperforms all prior generative methods on the ATLAS monomer benchmark, and the all-atom capabilities of AnewSampling enable close statistical alignment with ground-truth MD for evaluating atomic biomolecular interactions in protein-ligand dynamics. Furthermore, AnewSampling successfully recovers coupled ligand and side-chain motions in CDK2 systems, overcoming a major sampling hurdle inherent to conventional MD. AnewSampling enables rapid exploration of conformational landscapes prior to intensive simulations, elucidating fundamental biophysical mechanisms and accelerating the broader design of functional biomolecules.
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