增强扩散采样:利用扩散模型实现高效稀有事件采样与自由能计算 / Enhanced Diffusion Sampling: Efficient Rare Event Sampling and Free Energy Calculation with Diffusion Models
1️⃣ 一句话总结
这篇论文提出了一种名为‘增强扩散采样’的新方法,通过结合扩散模型与精确的偏置采样技术,高效解决了分子模拟中稀有事件(如蛋白质折叠)的采样难题,从而能够快速、准确地计算自由能等关键物理量。
The rare-event sampling problem has long been the central limiting factor in molecular dynamics (MD), especially in biomolecular simulation. Recently, diffusion models such as BioEmu have emerged as powerful equilibrium samplers that generate independent samples from complex molecular distributions, eliminating the cost of sampling rare transition events. However, a sampling problem remains when computing observables that rely on states which are rare in equilibrium, for example folding free energies. Here, we introduce enhanced diffusion sampling, enabling efficient exploration of rare-event regions while preserving unbiased thermodynamic estimators. The key idea is to perform quantitatively accurate steering protocols to generate biased ensembles and subsequently recover equilibrium statistics via exact reweighting. We instantiate our framework in three algorithms: UmbrellaDiff (umbrella sampling with diffusion models), $\Delta$G-Diff (free-energy differences via tilted ensembles), and MetaDiff (a batchwise analogue for metadynamics). Across toy systems, protein folding landscapes and folding free energies, our methods achieve fast, accurate, and scalable estimation of equilibrium properties within GPU-minutes to hours per system -- closing the rare-event sampling gap that remained after the advent of diffusion-model equilibrium samplers.
增强扩散采样:利用扩散模型实现高效稀有事件采样与自由能计算 / Enhanced Diffusion Sampling: Efficient Rare Event Sampling and Free Energy Calculation with Diffusion Models
这篇论文提出了一种名为‘增强扩散采样’的新方法,通过结合扩散模型与精确的偏置采样技术,高效解决了分子模拟中稀有事件(如蛋白质折叠)的采样难题,从而能够快速、准确地计算自由能等关键物理量。
源自 arXiv: 2602.16634