论文标题
通过转变后分叉增强了自由能曲线的采样
Enhanced Sampling for Free Energy Profiles with Post-Transition-State Bifurcations
论文作者
论文摘要
我们提出了一种使用基于脾气敏感的元动力学的增强的采样方法，通过过渡后分叉探索化学反应的自由能景观。消除了对计算昂贵的DFT级的需求，我们通过利用自由能扰动方案和深度学习估计器来获得准确的能量学，以获得底物构型的单点能量。使用一对易于解释的集体变量，我们提出了与谐波过渡状态理论计算以及分叉清晰可见的定量自由能表面。我们以SPNF催化的Diels-Alder反应的示例来证明我们的方法，该反应是一种环加成反应，其中转变后分叉导致[4+2]以及[6+4]环载体。我们获得了不同立体化学反应途径的自由能景观，并表征相关反应通道之间的机械连续性，而无需明确搜索相关的过渡状态结构。
We present a method to explore the free energy landscapes of chemical reactions with post-transition-state bifurcations using an enhanced sampling method based on well-tempered metadynamics. Obviating the need for computationally expensive DFT-level ab initio molecular dynamics simulations, we obtain accurate energetics by utilizing a free energy perturbation scheme and deep learning estimator for the single-point energies of substrate configurations. Using a pair of easily interpretable collective variables, we present a quantitative free energy surface that is compatible with harmonic transition state theory calculations and in which the bifurcations are clearly visible. We demonstrate our approach with the example of the SpnF-catalyzed Diels-Alder reaction, a cycloaddition reaction in which post-transition-state bifurcation leads to the [4+2] as well as the [6+4] cycloadduct. We obtain the free energy landscapes for different stereochemical reaction pathways and characterize the mechanistic continuum between relevant reaction channels without explicitly searching for the pertinent transition state structures.
