A Rigorous Method for Identifying a One-Dimensional Reaction Coordinate in Complex Molecules
A Rigorous Method for Identifying a One-Dimensional Reaction Coordinate in Complex Molecules
复制标题
识别复杂分子中一维反应坐标的严格方法
DOI：
10.1021/acs.jctc.2c00132
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发表时间：
2022
影响因子：
5.5
通讯作者：
Ma, Ao
中科院分区：
文献类型：
--
作者：
Wu, Shanshan;Li, Huiyu;Ma, Ao
了解功能蛋白质动力学的机制对于理解蛋白质功能至关重要。反应坐标（RC）是蛋白质动力学中的一个中心话题，而圣杯是找到可以完全确定提交者（即，构型空间中的反应概率）。我们提出了一种新的方法，第一次，使用一个基本的力学算子，广义功泛函，以确定严格的1D-RC在复杂的分子。对于典型的生物分子异构化反应，通过当前方法鉴定的1D-RC可以以远超过通过先前方法实现的准确度确定提交者。这种方法只需要适度的计算成本，可以很容易地应用于大分子。最重要的是，广义功泛函是功能蛋白质动力学中集体性的物理决定因素，并提供了一个连接蛋白质结构与功能的初步路线图。
Understanding the mechanism of functional protein dynamics is critical to understanding protein functions. Reaction coordinate (RC) is a central topic in protein dynamics, and the grail is to find the one-dimensional RC (1D-RC) that can fully determine the value of a committor (i.e., the reaction probability in configuration space) for any protein configuration. We present a new method that, for the first time, uses a fundamental mechanical operator, the generalized work functional, to identify the rigorous 1D-RC in complex molecules. For a prototypical biomolecular isomerization reaction, the 1D-RC identified by the current method can determine the committor with an accuracy far exceeding what was achieved by previous methods. This method only requires modest computational cost and can be readily applied to large molecules. Most importantly, the generalized work functional is the physical determinant of the collectivity in functional protein dynamics and provides a tentative roadmap that connects the structure of a protein to its function.