Simulations of Calcium Selectivity and Binding

通道是一种蛋白质，在它们的中间有孔，控制着一系列的生物功能， 通过控制带电原子（离子）穿过绝缘膜的运动来控制健康和疾病。 离子是带电的球体，通过扩散在通道中移动，并在电场中漂移。明渠 允许膜在不同种类的离子之间进行选择：选择性是生命的“定义特征”，至少在 教科书渠道结构不会改变，一旦他们是开放的，所以我们可以尝试了解和控制 使用物理科学的语言和数学的通道的选择性，没有特殊的地址 蛋白质的性质或它们的构象变化。 通道壁上有大量的永久电荷，这些电荷是由通道上的自然电荷产生的。 形成蛋白质的氨基酸永久性收费必须伴随着（几乎）等量的 相反的移动的电荷。离子和通道是不可分割的，根据一个基本的法律，电力，所谓的" 电中性原理”。数量密度（即，离子在通道中的浓度）非常高，通常为约20 M（纯水为-55 M），因此，将通道中的离子视为物理化学家认为离子中的离子是合乎逻辑的。 浓缩溶液。令人惊讶的是，这样简单的理论却能解释许多复杂的高度选择性的性质 而不调用其他可能存在的特殊力量。进化似乎利用拥挤 电荷产生选择性，比任何其他东西都重要。 我们建议研究高选择性的钙通道与模拟的真实的蛋白质，含有拥挤的 消费标准.我们将使用合成的蛋白质具有拥挤的电荷和计算这些通道的选择性 用几种不同的方法，比较结果与以前的工作，使用较不完善的模型， 系统我们将使用这些计算来设计高选择性的钙通道的医疗和技术 兴趣模拟将表明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.