Maggiora Gerald M, Bajorath Jürgen
University of Arizona BIO5 Institute, 1657 East Helen Street, Tucson, AZ, 85721, USA,
J Comput Aided Mol Des. 2014 Aug;28(8):795-802. doi: 10.1007/s10822-014-9760-0. Epub 2014 Jun 13.
The concept of chemical space is playing an increasingly important role in many areas of chemical research, especially medicinal chemistry and chemical biology. It is generally conceived as consisting of numerous compound clusters of varying sizes scattered throughout the space in much the same way as galaxies of stars inhabit our universe. A number of issues associated with this coordinate-based representation are discussed. Not the least of which is the continuous nature of the space, a feature not entirely compatible with the inherently discrete nature of chemical space. Cell-based representations, which are derived from coordinate-based spaces, have also been developed that facilitate a number of chemical informatic activities (e.g., diverse subset selection, filling 'diversity voids', and comparing compound collections).These representations generally suffer the 'curse of dimensionality'. In this work, networks are proposed as an attractive paradigm for representing chemical space since they circumvent many of the issues associated with coordinate- and cell-based representations, including the curse of dimensionality. In addition, their relational structure is entirely compatible with the intrinsic nature of chemical space. A description of the features of these chemical space networks is presented that emphasizes their statistical characteristics and indicates how they are related to various types of network topologies that exhibit random, scale-free, and/or 'small world' properties.
化学空间的概念在化学研究的许多领域，尤其是药物化学和化学生物学中发挥着越来越重要的作用。它通常被认为是由众多大小各异的化合物簇组成，这些簇分散在整个空间中，就如同恒星星系存在于我们的宇宙中一样。本文讨论了与这种基于坐标的表示相关的一些问题。其中最重要的是空间的连续性，这一特征与化学空间固有的离散性质并不完全兼容。基于坐标空间衍生出的基于细胞的表示方法也已得到发展，它有助于开展多种化学信息学活动（例如，多样性子集选择、填补“多样性空白”以及比较化合物集合）。这些表示方法通常会遭遇“维度诅咒”。在这项工作中，网络被提议作为一种有吸引力的表示化学空间的范式，因为它们规避了许多与基于坐标和基于细胞的表示相关的问题，包括维度诅咒。此外，它们的关系结构与化学空间的内在性质完全兼容。本文介绍了这些化学空间网络的特征，强调了它们的统计特性，并指出了它们与呈现随机、无标度和/或“小世界”性质的各种网络拓扑结构之间的关系。
