Multiple Scales in the Simulation of Ion Channels and Proteins.
Multiple Scales in the Simulation of Ion Channels and Proteins.
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DOI：
10.1021/jp106760t
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发表时间：
2010-10-21
期刊：
影响因子：
--
通讯作者：
Eisenberg B
中科院分区：
文献类型：
--
作者：
Eisenberg B
生命过程的计算为人类的日常生活带来了巨大的希望，也给物理学家带来了巨大的挑战。模拟分子动力学作为结构生物学的自然延伸，对生物学家有很大的吸引力。一旦生物学家看到一个结构，她/他就想看到它移动。分子生物学已经证明，少量的原子，有时甚至一个信使离子，如钙离子，就可以在细胞、器官、组织和生物体的尺度上控制生物功能。蛋白质通道和酶中高度集中的离子--数密度为~20M--决定了生命系统的许多特征，就像电极附近的高浓度离子决定了电化学系统的许多特征一样。在这里，我们面对离子尺度差异的现实。结果表明，模拟所有生物细胞原子所需的尺度差为：线性维度107个，三维1021个，分辨率109个，时间1011个，粒子数1013个(处理钙离子浓度)。如果模拟要处理大多数生物功能，则必须同时处理这些标尺。在大多数情况下，生物功能一下子跨越了所有这些生物。我们建议使用显式多尺度分析而不是所有尺度的隐式模拟的计算方法。该方法基于刘春提出的处理复杂流体的能量变分原理EnVarA。变分方法自动处理多个相互作用的分量和尺度。当系统中增加一个额外的组件时，得到的欧拉-拉格朗日方程会自动改变形式--仅通过代数--而不需要额外的未知参数。多方面的相互作用是所产生的方程的解。我们建议将离子溶液视为具有简单组分的复杂流体。EnVarA很容易计算出以组件相互作用为主的高度集中的解决方案。成功计算集中在特定位置的离子可能是理解生物和电化学系统定义特征的重要一步。事实上，计算蛋白质和核酸附近的离子对于分子生物学和化学技术的重要性，可能与计算空穴和电子对于我们的半导体和数字技术的重要性一样重要。
Computation of living processes creates great promise for the everyday life of mankind and great challenges for physical scientists. Simulations molecular dynamics have great appeal to biologists as a natural extension of structural biology. Once a biologist sees a structure, she/he wants to see it move. Molecular biology has shown that a small number of atoms, sometimes even one messenger ion, like Ca2+, can control biological function on the scale of cells, organs, tissues, and organisms. Enormously concentrated ions—at number densities of ~20 M—in protein channels and enzymes are responsible for many of the characteristics of living systems, just as highly concentrated ions near electrodes are responsible for many of the characteristics of electrochemical systems. Here we confront the reality of the scale differences of ions. We show that the scale differences needed to simulate all the atoms of biological cells are 107 in linear dimension, 1021 in three dimensions, 109 in resolution, 1011 in time, and 1013 in particle number (to deal with concentrations of Ca2+). These scales must be dealt with simultaneously if the simulation is to deal with most biological functions. Biological function extends across all of them, all at once in most cases. We suggest a computational approach using explicit multiscale analysis instead of implicit simulation of all scales. The approach is based on an energy variational principle EnVarA introduced by Chun Liu to deal with complex fluids. Variational methods deal automatically with multiple interacting components and scales. When an additional component is added to the system, the resulting Euler Lagrange field equations change form automatically—by algebra alone—without additional unknown parameters. Multifaceted interactions are solutions of the resulting equations. We suggest that ionic solutions should be viewed as complex fluids with simple components. Highly concentrated solutions—dominated by interactions of components—are easily computed by EnVarA. Successful computation of ions concentrated in special places may be a significant step to understanding the defining characteristics of biological and electrochemical systems. Indeed, computing ions near proteins and nucleic acids may prove as important to molecular biology and chemical technology as computing holes and electrons has been to our semiconductor and digital technology.
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DOI：
10.1085/jgp.200910211
发表时间：
2009-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Boda D;Valiskó M;Henderson D;Eisenberg B;Gillespie D;Nonner W
通讯作者：
Nonner W
影响因子：
2.9
作者：
Antosiewicz, J;McCammon, JA;Gilson, MK
通讯作者：
Gilson, MK
影响因子：
3.4
作者：
Boda, Dezso;Nonner, Wolfgang;Gillespie, Dirk
通讯作者：
Gillespie, Dirk
影响因子：
3.4
作者：
Bostick, David L.;Brooks, Charles L., III
通讯作者：
Brooks, Charles L., III
DOI：
10.1073/pnas.0914109107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Chakrapani, Sudha;Sompornpisut, Pornthep;Perozo, Eduardo
通讯作者：
Perozo, Eduardo