用预训练变分桥统一生成分子轨迹,高效且保真。
Unified Biomolecular Trajectory Generation via Pretrained Variational Bridge
- 通过编码器-解码器结构将初始构型映射到噪声潜空间,逐步迁移至目标状态。
- 在蛋白质和复合物上复现了与分子动力学一致的热力学与动力学特征。
- 支持跨域结构知识利用,适合需要快速生成高精度轨迹的研究者。
分子动力学模拟虽能以全原子分辨率刻画分子行为,但受限于计算成本。近年来涌现的深度生成模型试图通过粗粒化时间步学习动力学以实现高效轨迹生成,但普遍存在跨系统泛化能力差,或因轨迹数据结构多样性不足,难以充分挖掘结构信息提升生成保真度的问题。本文提出预训练变分桥(PVB),采用编码器-解码器架构,将初始结构映射至带噪声的潜空间,并通过增强桥接匹配实现向阶段特异性目标的传输。该方法统一训练单结构与配对轨迹数据,实现跨训练阶段的跨域结构知识共享。针对蛋白-配体复合物,进一步引入基于伴随匹配的强化学习优化策略,加速向全结合态演化,支持对接构象的高效后优化。在蛋白质及蛋白-配体复合物上的实验表明,PVB能够忠实再现分子动力学中的热力学与动力学可观测量,同时具备稳定高效的生成动态。
原文摘要 · Abstract (English)
Molecular Dynamics (MD) simulations provide a fundamental tool for characterizing molecular behavior at full atomic resolution, but their applicability is severely constrained by the computational cost. To address this, a surge of deep generative models has recently emerged to learn dynamics at coarsened timesteps for efficient trajectory generation, yet they either generalize poorly across systems or, due to limited molecular diversity of trajectory data, fail to fully exploit structural information to improve generative fidelity. Here, we present the Pretrained Variational Bridge (PVB) in an encoder-decoder fashion, which maps the initial structure into a noised latent space and transports it toward stage-specific targets through augmented bridge matching. This unifies training on both single-structure and paired trajectory data, enabling consistent use of cross-domain structural knowledge across training stages. Moreover, for protein-ligand complexes, we further introduce a reinforcement learning-based optimization via adjoint matching that speeds progression toward the holo state, which supports efficient post-optimization of docking poses. Experiments on proteins and protein-ligand complexes demonstrate that PVB faithfully reproduces thermodynamic and kinetic observables from MD while delivering stable and efficient generative dynamics.
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