Jennings Andy, Tennant Mike
Takeda San Diego, 10410 Science Center Drive, San Diego, California 92121, USA.
J Chem Inf Model. 2007 Sep-Oct;47(5):1829-38. doi: 10.1021/ci600549q. Epub 2007 Sep 8.
Molecular shape and electrostatic distribution play a crucial role in enzyme and receptor recognition and contribute extensively to binding affinity. Molecular similarity and bioisosterism are much-discussed topics in medicinal chemistry. Many molecular representations and similarity metrics are available to help drug discovery, and activities such as compound hit explosion and library design can be undertaken using them. The quality of the resulting compound series is highly dependent upon the molecular representation and similarity metric used. We have used a range of software to investigate whether molecules can be represented and compared effectively using measures of three-dimensional shape and electrostatic distribution ("electroforms"). We find that these descriptors allow for the assessment of molecular similarities using standard molecular visualization tools and offer a method for comparing molecules that may be considered superior to other methods.
分子形状和静电分布在酶和受体识别中起着关键作用，并对结合亲和力有广泛贡献。分子相似性和生物电子等排体是药物化学中备受讨论的话题。有许多分子表示法和相似性度量可用于帮助药物发现，并且可以使用它们进行诸如化合物命中扩展和库设计等活动。所得化合物系列的质量高度依赖于所使用的分子表示法和相似性度量。我们使用了一系列软件来研究是否可以使用三维形状和静电分布的度量（“电子形式”）有效地表示和比较分子。我们发现这些描述符允许使用标准分子可视化工具评估分子相似性，并提供一种比较分子的方法，这种方法可能被认为优于其他方法。
