Computing committors via Mahalanobis diffusion maps with enhanced sampling data
Computing committors via Mahalanobis diffusion maps with enhanced sampling data
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DOI：
10.1063/5.0122990
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
Luke S. Evans;M. Cameron;P. Tiwary
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文献类型：
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作者：
Luke S. Evans;M. Cameron;P. Tiwary
对蛋白质折叠和分子构象变化等现象的研究是化学物理学的中心主题。分子动力学（MD）模拟是研究生物分子中过渡过程的主要工具，但它受到感兴趣的过程和原子振动之间的巨大时间尺度差距的阻碍，这决定了时间步长。因此，必须将联合收割机MD模拟与其他技术相结合，以量化在大时间尺度上发生的过渡过程。在这项工作中，Mahalanobis内核的扩散映射，一个无网格的方法近似的后向Kolmogorov算子（BKO）的集体变量，升级到标准的增强采样技术，如元自适应。由此产生的算法，我们称之为目标措施Mahalanobis扩散图（tm-mmap），是适合于一个中等数量的集体变量，其中一个可以近似的扩散张量和自由能。施加适当的边界条件允许使用近似的BKO来求解提交函数，并利用过渡路径理论来找到描绘过渡通道和过渡速率的无功电流。所提出的算法，tm-mmap，进行了测试的二维Moro-Cardin双井系统与位置相关的扩散系数和丙氨酸二肽在两个集体变量，其中的提交人，反应电流，和过渡率进行比较，通过有限元法（FEM）计算。最后，TM-MMAP适用于丙氨酸二肽在四个集体变量，其中使用有限元是不可行的。
The study of phenomena such as protein folding and conformational changes in molecules is a central theme in chemical physics. Molecular dynamics (MD) simulation is the primary tool for the study of transition processes in biomolecules, but it is hampered by a huge timescale gap between the processes of interest and atomic vibrations that dictate the time step size. Therefore, it is imperative to combine MD simulations with other techniques in order to quantify the transition processes taking place on large timescales. In this work, the diffusion map with Mahalanobis kernel, a meshless approach for approximating the Backward Kolmogorov Operator (BKO) in collective variables, is upgraded to incorporate standard enhanced sampling techniques, such as metadynamics. The resulting algorithm, which we call the target measure Mahalanobis diffusion map (tm-mmap), is suitable for a moderate number of collective variables in which one can approximate the diffusion tensor and free energy. Imposing appropriate boundary conditions allows use of the approximated BKO to solve for the committor function and utilization of transition path theory to find the reactive current delineating the transition channels and the transition rate. The proposed algorithm, tm-mmap, is tested on the two-dimensional Moro-Cardin two-well system with position-dependent diffusion coefficient and on alanine dipeptide in two collective variables where the committor, the reactive current, and the transition rate are compared to those computed by the finite element method (FEM). Finally, tm-mmap is applied to alanine dipeptide in four collective variables where the use of finite elements is infeasible.