Influence of Grid Spacing in Poisson-Boltzmann Equation Binding Energy Estimation.
Influence of Grid Spacing in Poisson-Boltzmann Equation Binding Energy Estimation.
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DOI：
10.1021/ct300765w
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发表时间：
2013-08-13
影响因子：
5.5
通讯作者：
Fenley, Marcia O.
中科院分区：
文献类型：
--
作者：
Harris, Robert C.;Boschitsch, Alexander H.;Fenley, Marcia O.
基于网格的泊松-玻尔兹曼 (PB) 方程求解器通常用于估计静电结合 (ΔΔGel) 和溶剂化 (ΔGel) 自由能。这种估计的准确性受到从有限差分近似到 PB 方程的网格离散化误差的影响。在这里，我们发现 ΔΔGel 中的网格离散化误差比 ΔGel 中的网格离散化误差更显着，并且可以分为两部分：（i）与网格相对定位相关的误差和（ii）与网格间距相关的系统误差。对于分子力学 PB 表面积、MM-PBSA 等通过对分子构象集合进行平均来预测静电结合自由能的方法，系统误差尤其重要。虽然对多个构象进行平均可以控制与网格放置相关的误差，但它不会消除系统误差，只能通过减小网格间距来控制。本研究表明，广泛使用的 0.5 Å 网格间距会在 ΔΔGel 中产生不可接受的误差，尽管其对 ΔGel 的预测对于此处考虑的情况来说是足够的。尽管两种网格离散化误差通常都随着网格间距的增加而增加，但这些误差的相对大小根据溶质-溶剂介电边界的定义而有所不同。本研究中使用的高斯表面上的网格离散化误差通常比排除溶剂或范德华表面上的网格离散化误差更小，这两种表面都包含更多的表面不连续性（例如，尖锐的边缘和尖点）。此外，所有三个分子表面都会收敛到非常不同的 ΔΔGel 估计值。
Grid-based solvers of the Poisson-Boltzmann, PB, equation are routinely used to estimate electrostatic binding, ΔΔGel, and solvation, ΔGel, free energies. The accuracies of such estimates are subject to grid discretization errors from the finite difference approximation to the PB equation. Here, we show that the grid discretization errors in ΔΔGel are more significant than those in ΔGel, and can be divided into two parts: (i) errors associated with the relative positioning of the grid and (ii) systematic errors associated with grid spacing. The systematic error in particular is significant for methods, such as the molecular mechanics PB surface area, MM-PBSA, approach that predict electrostatic binding free energies by averaging over an ensemble of molecular conformations. Although averaging over multiple conformations can control for the error associated with grid placement, it will not eliminate the systematic error, which can only be controlled by reducing grid spacing. The present study indicates that the widely-used grid spacing of 0.5 Å produces unacceptable errors in ΔΔGel, even though its predictions of ΔGel are adequate for the cases considered here. Although both grid discretization errors generally increase with grid spacing, the relative sizes of these errors differ according to the solute-solvent dielectric boundary definition. The grid discretization errors are generally smaller on the Gaussian surface used in the present study than on either the solvent-excluded or van der Waals surfaces, which both contain more surface discontinuities (e.g., sharp edges and cusps). Additionally, all three molecular surfaces converge to very different estimates of ΔΔGel.
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影响因子：
5.5
作者：
Fenley, Marcia O.;Mascagni, Michael;McClain, James;Silalahi, Alexander R. J.;Simonov, Nikolai A.
通讯作者：
Simonov, Nikolai A.
影响因子：
3
作者：
Boschitsch, Alexander H.;Fenley, Marcia O.
通讯作者：
Fenley, Marcia O.
影响因子：
3
作者：
Feig, M;Onufriev, A;Brooks, CL
通讯作者：
Brooks, CL
影响因子：
7.3
作者：
Nicholls, Anthony;Mobley, David L.;Pande, Vijay S.
通讯作者：
Pande, Vijay S.
影响因子：
3
作者：
Grant, JA;Pickup, BT;Nicholls, A
通讯作者：
Nicholls, A