Chen Duan, Wei Guo-Wei
Department of Mathematics, Michigan State University, East Lansing, MI 48824, USA.
Commun Comput Phys. 2013 Jan 1;13(1):285-324. doi: 10.4208/cicp.050511.050811s. Epub 2012 Jun 12.
Proton transport is one of the most important and interesting phenomena in living cells. The present work proposes a multiscale/multiphysics model for the understanding of the molecular mechanism of proton transport in transmembrane proteins. We describe proton dynamics quantum mechanically via a density functional approach while implicitly model other solvent ions as a dielectric continuum to reduce the number of degrees of freedom. The densities of all other ions in the solvent are assumed to obey the Boltzmann distribution. The impact of protein molecular structure and its charge polarization on the proton transport is considered explicitly at the atomic level. We formulate a total free energy functional to put proton kinetic and potential energies as well as electrostatic energy of all ions on an equal footing. The variational principle is employed to derive nonlinear governing equations for the proton transport system. Generalized Poisson-Boltzmann equation and Kohn-Sham equation are obtained from the variational framework. Theoretical formulations for the proton density and proton conductance are constructed based on fundamental principles. The molecular surface of the channel protein is utilized to split the discrete protein domain and the continuum solvent domain, and facilitate the multiscale discrete/continuum/quantum descriptions. A number of mathematical algorithms, including the Dirichlet to Neumann mapping, matched interface and boundary method, Gummel iteration, and Krylov space techniques are utilized to implement the proposed model in a computationally efficient manner. The Gramicidin A (GA) channel is used to demonstrate the performance of the proposed proton transport model and validate the efficiency of proposed mathematical algorithms. The electrostatic characteristics of the GA channel is analyzed with a wide range of model parameters. The proton conductances are studied over a number of applied voltages and reference concentrations. A comparison with experimental data verifies the present model predictions and validates the proposed model.
质子传输是活细胞中最重要且最有趣的现象之一。本研究提出了一种多尺度/多物理场模型,用于理解跨膜蛋白中质子传输的分子机制。我们通过密度泛函方法对质子动力学进行量子力学描述,同时将其他溶剂离子隐式建模为介电连续体,以减少自由度的数量。假设溶剂中所有其他离子的密度服从玻尔兹曼分布。在原子水平上明确考虑了蛋白质分子结构及其电荷极化对质子传输的影响。我们构建了一个总自由能泛函,将质子动能、势能以及所有离子的静电能置于同等地位。运用变分原理推导质子传输系统的非线性控制方程。从变分框架中得到广义泊松 - 玻尔兹曼方程和科恩 - 沈方程。基于基本原理构建了质子密度和质子电导率的理论公式。利用通道蛋白的分子表面来划分离散的蛋白质区域和连续的溶剂区域,并促进多尺度离散/连续/量子描述。运用了多种数学算法,包括狄利克雷到诺伊曼映射、匹配界面和边界方法、古梅尔迭代以及克雷洛夫空间技术,以高效的计算方式实现所提出的模型。使用短杆菌肽A(GA)通道来展示所提出的质子传输模型的性能,并验证所提出数学算法的效率。在广泛的模型参数范围内分析了GA通道的静电特性。研究了在多个施加电压和参考浓度下的质子电导率。与实验数据的比较验证了本模型的预测,并验证了所提出的模型。