Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850, USA.
J Chem Phys. 2011 Apr 7;134(13):134107. doi: 10.1063/1.3571441.
The free energy of a molecular system can, at least in principle, be computed by thermodynamic perturbation from a reference system whose free energy is known. The convergence of such a calculation depends critically on the conformational overlap between the reference and the physical systems. One approach to defining a suitable reference system is to construct it from the one-dimensional marginal probability distribution functions (PDFs) of internal coordinates observed in a molecular simulation. However, the conformational overlap of this reference system tends to decline steeply with increasing dimensionality, due to the neglect of correlations among the coordinates. Here, we test a reference system that can account for pairwise correlations among the internal coordinates, as captured by their two-dimensional marginal PDFs derived from a molecular simulation. Incorporating pairwise correlations in the reference system is found to dramatically improve the convergence of the free energy estimates relative to the first-order reference system, due to increased conformational overlap with the physical distribution.
分子系统的自由能至少在原则上可以通过热力学微扰从自由能已知的参考系统计算得出。这种计算的收敛性在很大程度上取决于参考系统和物理系统之间的构象重叠。定义合适的参考系统的一种方法是从分子模拟中观察到的内部坐标的一维边缘概率分布函数（PDF）构建。然而，由于忽略了坐标之间的相关性，该参考系统的构象重叠随着维度的增加急剧下降。在这里，我们测试了一种参考系统，该系统可以解释内部坐标之间的二阶相关性，这是通过从分子模拟中得到的二维边缘 PDF 来捕捉的。在参考系统中包含二阶相关性会显著提高自由能估计的收敛性，因为与物理分布的构象重叠增加了。
