Multiple Scales in the Simulation of Ion Channels and Proteins
Bob Eisenberg
备注：
arXiv admin note: text overlap with arXiv:1009.1786; AUTHOR NOTE: Reader, please check extent of overlap for yourself; Revision 2 change only on title page, to show arXiv reference
发表信息：
Journal of Physical Chemistry C (2010) 114 20719-20733
Computation of biological processes creates great promise for everyday life and great challenges for physical scientists. Simulations of molecular dynamics appeal to biologists as a natural extension of structural biology. Once biologists see a structure, they want to see it move. Molecular biology shows that a few atoms, often messenger ions like Ca$^{2+}$, control biological function on the scale of cells, sometimes organisms. Enormously concentrated ions (~20 M) in protein channels and enzymes can control important characteristics of living systems, just as highly concentrated ions near electrodes control important characteristics of electrochemical systems. The scale differences needed to simulate all the atoms of biological cells are $10^7$ in linear dimension, $10^{21}$ in three dimensions, $10^{9}$ in resolution, $10^{11}$ in time, and $10^{13}$ in particle number (to deal with concentrations of Ca$^{2+}$). $\mathbf{These}$ $\mathbf{scales}$ $\mathbf{must}$ $\mathbf{be}$ $\mathbf{dealt}$ $\mathbf{with}$ $\mathbf{simultaneously}$ if the simulation is to deal with most biological functions. We suggest a computational approach using explicit multiscale analysis instead of implicit simulation of all scales. Successful computation of ions concentrated in special places may be a significant step to understanding the defining characteristics of biological and electrochemical systems.
水中的离子在生物学中很重要，从分子到器官。传统上，水中的离子被视为理想气体中的理想非相互作用粒子。离子的过剩自由能为零。当时没有数学方法来处理流动，或者与离子或边界的相互作用。非经典的方法是必要的，因为在生物条件下的离子流动和相互作用。一种离子的浓度梯度可以驱动另一种离子的流动，即使在本体溶液中也是如此。一个变分多尺度的方法是需要处理的相互作用和流动。最近开发的能量耗散系统的变分方法允许数学上一致的治疗生物离子钠，钾，钙和氯，因为它们相互作用和流动。相互作用产生大量的过剩自由能，支配蛋白质活性位点、通道和核酸中及其附近的高浓度离子的性质：离子的数密度通常超过10 M。在如此拥挤的区域中，离子彼此之间以及与周围的蛋白质之间强烈地相互作用。非理想的行为已被经典地归因于由蛋白质构象变化介导的变构相互作用。离子-离子相互作用存在于拥挤的解决方案-独立的蛋白质的构象变化-可能会改变的解释变构现象。所有原子的计算是多尺度方法的流行替代方案。这样的计算包含着巨大的挑战。生物系统存在于与原子运动截然不同的尺度上。生物系统存在于离子混合物（细胞外/细胞内溶液）中，并且通常涉及信使离子的流动和痕量浓度（例如，10-7 M Ca 2+）。能量变分方法可以处理这些特征性质的生物系统，而我们等待成熟和校准的所有原子模拟的离子混合物和二价。
A robust methodology for inferring physiology of a protein family: application to K+-ion channel family
We are interested in the subtle variations of function among the members of a protein family. A protein family is usually subdivided into subfamilies based on functional differences. Existence of this functional diversity is essential for the successful performance of physiological roles expected of the family. This presents a unique problem: there must be preservation of the active site; simultaneously there should be specificity of protein action according to subfamily. Though the classification into subfamilies is by no means a formalized one, it is most times based on the character of regu…
