Simulations of Calcium Selectivity and Binding

通道是一种中间有孔的蛋白质，它控制着体内大量的生物功能 通过控制带电原子(离子)在其他绝缘膜上的运动来控制健康和疾病。 离子是带电的球体，在电场中通过扩散和漂移通过通道。畅通航道 允许膜在不同种类的离子之间进行选择：选择性是生命的一个“决定性特征”，至少在 教科书。渠道结构一旦开放就不会改变，因此我们可以尝试了解和控制 使用物理科学的语言和数学的频道的选择性，而不涉及特殊的 蛋白质的性质或它们的构象变化。 渠道的墙壁上有大量的永久电荷，这些电荷是由 构成蛋白质的氨基酸。永久押记必须附有(几乎)等量的 相反的移动电荷。根据电学的基本定律，离子和通道是密不可分的 “电中性原理”。离子在通道中的数密度(即浓度)非常高，通常为-20 M(纯水是-55M)，所以物理化学家认为离子在通道中的方式是合乎逻辑的 浓缩溶液。令人惊讶的是，这些简单的理论解释了许多复杂的高度选择性的性质 在没有调用其他可能存在的特种部队的情况下。进化论似乎用拥挤 收费是为了生产选择性，而不是其他东西。 我们建议通过模拟包含拥挤的真实蛋白质来研究高度选择性的钙通道 充电。我们将使用合成的蛋白质来产生密集电荷，并计算这些通道的选择性 使用几种不同的方法，将结果与使用较不精细的模型的先前工作进行比较 系统。我们将利用这些计算来设计具有高度选择性的医疗和技术的钙通道 利息。模拟将提出在理论和设计上需要改进的地方。

Channels are proteins with holes down their middle that control an enormous range of biological function in health and disease by controlling movement of charged atoms (ions) across otherwise insulating membranes. Ions are charged spheres that move through channels by diffusion and drift in the electric field. Open channels allow membranes to select between different kinds of ions: selectivity is a 'defining feature' of life, at least in textbooks. Channel structure does not change once they are open and so we can try to understand and control selectivity of channels using the language and mathematics of physical science, without addressingspecial properties of proteins or their conformation changes. Channels have large amounts of permanent electrical charge on their walls, created by the natural charge on the amino acids forming the protein. The permanent charge must be accompanied by (nearly) equal amounts of opposite mobile charge. Ions and channels are inseparable, according to a basic law of electricity, called 'the principle of electroneutrality'. The number density (i.e., concentration) of ions in channels is very high, often -20 M (pure water is -55 M), so it is logical to think of ions in channels the way physical chemists think of ions in concentrated solutions. Surprisingly, such simple theories acccount for many complex highly selective properties of calcium channels without invoking other special forces that might be present. Evolution seems to use crowded charge to produce selectivity, more than anything else. We propose to study highly selective calcium channels with simulations of real proteins that contain crowded charge. We will use proteins synthesized to have crowded charge and compute the selectivity of these channels with several different methods, comparing the results with previous work using less refined models of the system. We will use these computations to design highly selective Ca channels of medical and technological interest. The simulations will suggest what needs to be improved in theory and design.