2006 American Chemical Society Award for Computers in Chemical and Pharmaceutical Research - Of molecules and humans
2006 American Chemical Society Award for Computers in Chemical and Pharmaceutical Research - Of molecules and humans
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DOI：
10.1021/jm0608964
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发表时间：
2006-11-02
影响因子：
7.3
通讯作者：
Gasteiger, Johann
中科院分区：
文献类型：
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作者：
Gasteiger, Johann
分子结构与其生物活性之间关系的理解和建模是药物化学的中心主题。显然，化合物的生物活性不能直接通过分子结构的第一原理计算。在这种情况下，必须采取间接方法来找到化合物的分子结构与其生物活性之间的关系（图1）。首先，分子的结构必须用结构描述符来表示。然后，这些结构描述符用于建模的生物活性。这第二步要求一组分子及其相关的生物活性，以便应用归纳学习方法，如统计或模式识别方法或人工神经网络，以建立结构描述符和生物活性之间的关系。在本文中，我们将集中在第一步，分子的表示。在过去的几十年中，已经开发了各种各样的方法来获得分子的结构描述符。1-3我们在这里提出了一个排序方案，允许一个确定的复杂程度的结构表示。在这一奋进中，我们将比较分子和人类，两者都是具有表面的三维物体，具有不同类型的表面，具有手性部分，并且是柔性的（图2）。这种比较将使我们能够决定从某种类型的分子结构表示中可以期待什么样的结果，从而为手头的某个问题选择哪种结构表示提供指导。
The understanding and modeling of the relationships between the structure of a molecule and its biological activity are the central themes of medicinal chemistry. Clearly, the biological activity of a compound cannot directly be calculated by first principles from the molecular structure. In this situation, an indirect approach has to be taken to find a relationship between the molecular structure of a compound and its biological activity (Figure 1). First, the structure of a molecule has to be represented by structure descriptors. Then these structure descriptors are used for modeling the biological activity. This second step asks for a set of molecules and their associated biological activities in order to apply inductive learning methods such as statistical or pattern recognition methods or artificial neural networks to establish a relationship between the structure descriptors and the biological activity.In this article we will concentrate on the first step, the representation of molecules. In the past few decades a wide variety of methods have been developed to derive structure descriptors for a molecule. 1-3 We propose here an ordering scheme that allows one to determine the level of sophistication in structure representation. In this endeavor we will compare molecules with humans, both being three-dimensional objects having surfaces, having different types of surfaces, having chiral parts, and being flexible (Figure 2). This comparison will allow us to decide what results we can expect from a certain type of molecular structure representation and thus give guidelines on which structure representation to choose for a certain problem at hand.