MOLECULAR INTERACTIVE COLLABORATIVE ENVIRONMENTS (MICE): PROTEIN STRUCT

血红蛋白对氧的亲和力取决于氧气量 已经和分子结合在一起了。每个血红蛋白分子都可以结合在一起 四个氧分子。当没有氧结合时，亲和力是 低；当四个氧分子结合时，亲和力高。这 这意味着肺部的血红蛋白很容易携带氧气，而且 会携带氧气，直到它遇到氧气不足的区域 为了卸货，脱氧的低亲和力加速了这一过程 一种形式的血红蛋白。这一财产对人类生命至关重要。虽然 血红蛋白的氧合形式和脱氧形式的结构都是已知的 (和不同的)，没有人具体知道一个人的绑定是如何 氧分子直接影响其他三个位置的亲和力 在结构之间的构象方面有一个小的位移 彼此相对的刚体数量。我们的方法是基于 关于寻找原子间距离的集合，它们以前是相同的 在结构变化之后。我们已经将该方法应用于 并发现这样的描述提供了一种简单和 分析与以下方面有关的结构变化的合理框架 氧气结合。我们首先研究了阿尔法-贝塔半分子， 由血红蛋白中四个亚基中的两个组成，并形成了一种 1997年7月发表在《分子生物学杂志》上。我们现在已经完成了一个 两个α-β二聚体相互作用方式的分析 并在不同的事物之间找到意想不到的联系 准备工作。我们将继续这个项目，研究 氧和脱氧血红素性质之间的相互作用 来自量子力学研究的金·巴尔德里奇博士，以及刚性 这一模型的预测将通过与 圣路易斯华盛顿大学的加里·艾克斯教授。一位直接的 为研究血红蛋白而开发的方法的扩展是 确定两个蛋白质空间相似性的方法，处理如下 两条具有间隙和插入的空间曲线的同余问题。 这种方法已被用来对所有已知蛋白质进行结构比对 结果，与已知的序列同源性一致。它 空间一致性可能是一种强大的检测工具 意想不到的关系，因为它只取决于坐标和 在下一个拨款年度内为其分发软件。

Hemoglobin is an efficient oxygen carrier in blood because affinity of hemoglobin for oxygen depends on how much oxygen is already bound to the molecule. Each hemoglobin molecule can bind up to four oxygen molecules. When no oxygen is bound the affinity is low; when four oxygen molecules are bound, the affinity is high. This means that in the lungs hemoglobin is easily loaded with oxygen, and will carry that oxygen until it encounters an area of low oxygen tension, where the oxygen should be delivered. Once the oxygen starts to unload, the process is accelerated by the low affinity of the deoxy form of hemoglobin. This property is vital for human life. Although the structures of both oxy and deoxy forms of hemoglobin are known (and different), Nobody knows specifically how the binding of one oxygen molecule directly affects the affinity of the other three sites for oxygen. We have developed novel methods for describing the change in conformation between structures in terms of shifts of a small number of rigid bodies relative to one another. Our method is based on finding sets of interatomic distances, which are the same before and after the structural change. We have applied this method to hemoglobin and found that such a description provides a simple and plausible framework for analysis of the structural changes related to oxygen binding. We first examined the Alpha-Beta half molecule, composed of two of the four subunits in hemoglobin, and developed a description of the changes on oxygenation. This work was published in July 1997 in the Journal of Molecular Biology. We have now done an analysis of the ways in which the two Alpha-Beta dimers interact with one another, and find unexpected connections between the different binding sites in the molecule. A manuscript on this subject is in preparation. We will continue this project by studying the interaction between properties of oxy and deoxy heme as developed by Dr. Kim Baldridge from quantum mechanical studies, and the rigid bodies surrounding the heme pocket. Experimentally testable predictions of this model will be studied through a collaboration with Prof. Gary Ackers of Washington University in St. Louis. A direct extension of the methods developed for the study of hemoglobin is a method for determining spatial similarity of two proteins, treated as a problem of congruence of two space curves with gaps and insertions. This method has been used to structurally align all known protein kinases with results, which agree with known sequence homology. It appears that spatial congruence may be a powerful tool for detection of unexpected relationships, since it depends only on coordinates and not on sequence. We will explore this technique and develop distributable software for it during the next grant year.