MOLECULAR INTERACTIVE COLLABORATIVE ENVIRONMENTS (MICE): PROTEIN STRUCT

血红蛋白是血液中有效的氧载体， 血红蛋白对氧的亲和力取决于 已经与分子结合。 每一个血红蛋白分子 四个氧分子。 当没有氧被束缚时， 低;当四个氧分子结合时，亲和力高。 这 这意味着肺中的血红蛋白很容易携带氧气， 会携带氧气直到遇到低氧区 紧张，氧气应该输送到哪里。 一旦氧气开始 为了卸载，该过程被脱氧的低亲和力加速， 血红蛋白的形式。 这种特性对人类生命至关重要。 虽然 血红蛋白的氧合和脱氧形式的结构都是已知的 (and没有人确切地知道一个人的约束力如何 氧分子直接影响其他三个位点的亲和力 氧气。 我们已经开发了新的方法来描述这种变化 在结构之间的构象中， 相对于彼此的刚体的数量。 我们的方法是基于 找到原子间距离的集合， 在结构变化之后。 我们将这种方法应用于 血红蛋白，并发现这样的描述提供了一个简单的， 分析与发展有关的结构变化的合理框架 氧结合 我们首先研究了α-β半分子， 由血红蛋白四种亚基中的两种组成，并开发了一种 氧合变化的描述。 这项工作发表在 1997年7月发表在《分子生物学杂志》上。 我们现在已经做了一个 分析两种α-β二聚体与 彼此，并在不同的人之间找到意想不到的联系 分子中的结合位点。 关于这个问题的手稿在 准备. 我们将继续这项计划，研究 氧和脱氧血红素的性质之间的相互作用， 博士量子力学研究的金·鲍德里奇， 血红素袋周围的尸体 实验检验 该模型的预测将通过与 教授 圣路易斯华盛顿大学的加里·阿克斯说。 直接 血红蛋白研究方法的扩展是一种 用于确定两种蛋白质的空间相似性的方法， 两条带缺口和插入的空间曲线的叠合问题。 该方法已用于所有已知蛋白质的结构比对 激酶，结果与已知序列同源性一致。 它 似乎空间一致性可能是一个强大的工具， 意想不到的关系，因为它只依赖于坐标， 不是按顺序。 我们将探索这项技术， 在下一个资助年度为它提供可分发的软件。

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.