Generalized Langevin Methods for Calculating Transmembrane Diffusivity
Generalized Langevin Methods for Calculating Transmembrane Diffusivity
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DOI：
10.1021/acs.jctc.6b00747
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发表时间：
2016-11-01
影响因子：
5.5
通讯作者：
Rowley, Christopher N.
中科院分区：
文献类型：
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作者：
Gaalswyk, Kari;Awoonor-Williams, Ernest;Rowley, Christopher N.
溶质的膜渗透系数可以使用溶解度扩散模型来估计。该模型需要溶质沿沿着跨膜轴z移动时的扩散率分布（D（z））。广义朗之万方程提供了一种从简单的分子动力学模拟中计算位置相关扩散率的策略，其中溶质被谐波势限制在z坐标上的一系列位置。溶质的扩散率是从其相关函数计算的，该相关函数与溶质所经历的摩擦有关。Roux和Hummer分别从速度自相关函数（VACF）和位置自相关函数（PACF）推导出扩散系数的表达式。在这项工作中，这些方法进行了验证，通过计算H2O和O-2在均匀液体中的扩散系数。然后使用这些方法来计算跨膜扩散率曲线。VACF方法对恒温器力不太敏感，误差逐渐降低，但对谐波约束的弹簧常数更敏感。对于溶质通过脂质双层的渗透，使用这些方法计算的扩散系数提供了显着不同的结果。由于双层中的不均匀性，受约束的溶质的长寿命相关性可以导致在使用PACF方法时虚假的低扩散率。基于VACF的方法没有这个问题，并且预测双层内的扩散速率更高。
The membrane permeability coefficient of a solute can be estimated using the solubility diffusion model. This model requires the diffusivity profile (D(z)) of the solute as it moves along the transmembrane axis, z. The generalized Langevin equation provides one strategy for calculating position-dependent diffusivity from straightforward molecular dynamics simulations where the solute is restrained to a series of positions on the z-coordinate by a harmonic potential. The diffusivity of the solute is calculated from its correlation functions, which are related to the friction experienced by the solute. Roux and Hummer have derived expressions for the diffusion coefficient from the velocity autocorrelation function (VACF) and position autocorrelation function (PACF), respectively. In this work, these methods are validated by calculating the diffusivity of H2O and O-2 in homogeneous liquids. These methods are then used to calculate transmembrane diffusivity profiles. The VACF method is less sensitive to thermostat forces and has incrementally lower errors but is more sensitive to the spring constant of the harmonic restraint. For the permeation of a solute through a lipid bilayer, the diffusion coefficients calculated using these methods provided significantly different results. Long-lived correlations of the restrained solute due to inhomogeneities in the bilayer can result in spuriously low diffusivity when using the PACF method. The method based on the VACF does not have this issue and predicts higher rates of diffusion inside the bilayer.