分子转变过程，包括蛋白质折叠、别构效应和膜转运，是生物功能的核心，但其模拟难度极大。这些过程固有的稀有性使其超出了标准分子动力学模拟的能力范围，而增强采样策略不仅计算成本高昂，且往往依赖于任意选择的参数和变量，从而导致结果偏差1–3。

Molecular transitions, including protein folding, allostery and membrane transport, are central to biological functions, yet remain notoriously difficult to simulate. Their intrinsic rarity places them beyond the reach of standard molecular dynamics, whereas enhanced-sampling strategies are computationally demanding and often depend on arbitrarily chosen parameters and variables that bias outcomes1–3.