Calculation of Conformational Free Energies with the Focused Confinement Method
Calculation of Conformational Free Energies with the Focused Confinement Method
复制标题
聚焦约束法计算构象自由能
DOI：
10.1021/acs.jctc.9b00590
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发表时间：
2019
影响因子：
5.5
通讯作者：
Le Phan, Sang T.
中科院分区：
文献类型：
--
作者：
van der Vaart, Arjan;Orndorff, Paul B.;Le Phan, Sang T.
我们介绍了聚焦限制方法，反应坐标自由模拟方法的构象自由能的计算。这些是在一系列约束模拟中获得的，这些模拟将感兴趣的分子的一部分转换为独立的谐振子，从而导致混合的谐波-非谐波状态。结果表明，这些混合状态之间的自由能差可以很容易地计算通过建设嵌合轨迹。通过将约束集中在构象活性区域，该方法比传统的约束方法需要更少的约束模拟，从而简化了大型系统的处理。该方法的准确性和效率证明了隐式和显式溶剂化系统。
We introduce the focused confinement method, a reaction coordinate-free simulation approach for the calculation of conformational free energies. These are obtained in a series of restrained simulations that transform part of the molecule of interest to independent harmonic oscillators resulting in mixed harmonic–anharmonic states. It is shown that the free energy difference between these mixed states can be readily calculated through the construction of chimeric trajectories. By focusing the confinement to the conformationally active region, the method requires fewer restrained simulations than the traditional confinement method, which eases the treatment of large systems. The accuracy and efficiency of the method is demonstrated for implicitly and explicitly solvated systems.