用规则组合表示催化机制
Representing catalytic mechanisms with rule composition
摘要：
反应机理通常以基本步骤的顺序来表示，例如通过箭头推动来编码。我们提出了一种方法来表示这样的机制，使用图变换。在这个框架中，每个基本步骤都是修改分子图的规则，而机制是这些规则的序列。为了生成多步反应的紧凑表示，我们将各个步骤的规则组合成一个复合规则，提供了一种严格且完全自动化的粗粒度方法。虽然复合规则保留了执行机制所需的图形条件，但它也记录了有关通过比较educt和product而不可见的瞬态更改的信息。通过投影规则到一个单一的“覆盖图”，我们推广藤田的想法，一个想象的过渡结构从基本反应的复合反应。在酶催化反应的上下文中举例说明了覆盖图构造的效用。在第一个应用程序中，我们利用机制和催化位点图谱中的机制信息来构建数据库中列出的水解酶反应的重叠图。这些图指向酶和底物的催化缠结的光谱，不强调单一催化剂的概念，而是支持可以分布在酶和底物上的催化位点的集合。在第二个应用程序中，我们部署复合规则搜索Rhea数据库中已知或未知机制的反应，原则上，与复合规则所暗示的机制兼容。我们相信这项工作增加了图形转换形式主义的实用性，以自动化但富有洞察力的方式表示和推理化学。
英文摘要：
Reaction mechanisms are often presented as sequences of elementary steps, such as codified by arrow pushing. We propose an approach for representing such mechanisms using graph transformation. In this framework, each elementary step is a rule for modifying a molecular graph and a mechanism is a sequence of such rules. To generate a compact representation of a multi-step reaction, we compose the rules of individual steps into a composite rule, providing a rigorous and fully automated approach to coarse-graining. While the composite rule retains the graphical conditions necessary for the execution of a mechanism, it also records information about transient changes not visible by comparing educts and products. By projecting the rule onto a single "overlay graph", we generalize Fujita's idea of an Imaginary Transition Structure from elementary reactions to composite reactions. The utility of the overlay graph construct is exemplified in the context of enzyme-catalyzed reactions. In a first application, we exploit mechanistic information in the Mechanism and Catalytic Site Atlas to construct overlay graphs of hydrolase reactions listed in the database. These graphs point at a spectrum of catalytic entanglement of enzyme and substrate, de-emphasizing the notion of a singular catalyst in favor of a collection of catalytic sites that can be distributed across enzyme and substrate. In a second application, we deploy composite rules to search the Rhea database for reactions of known or unknown mechanism that are, in principle, compatible with the mechanisms implied by the composite rules. We believe this work adds to the utility of graph-transformation formalisms in representing and reasoning about chemistry in an automated yet insightful fashion.
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