Devereux Michael, Popelier Paul L A, McLay Iain M
Manchester Interdisciplinary Biocenter, 131 Princess Street, Manchester M1 7DN, Great Britain.
J Comput Chem. 2009 Jun;30(8):1300-18. doi: 10.1002/jcc.21146.
The goal of this work is to assess the scope and suitability of atomic and bond properties for use in a bioisostere fragment database. This database will contain fragment descriptors that can be used to represent portions of larger molecules and similarity in properties between fragments, which will then be used to find bioisosteric replacements in future work. Seventeen common organic fragments relevant to drug design featured as "linker groups" that were capped by two terminal groups. Each terminal group could be one of the set of 12 possible sets: 10 aromatic heterocycles, a phenyl ring, or an ethyl. This enabled a systematic investigation of the chemical environment, enriched with conformational flexibility within the linker group, for a total of 307 different atoms. Five different levels of theory were investigated. This work paves the way to the construction of a quantum mechanical bioisosteric fragment database, for which transferability of stored fragment properties is of fundamental importance.
这项工作的目标是评估原子和键性质在生物电子等排体片段数据库中的应用范围和适用性。该数据库将包含可用于表示较大分子部分以及片段间性质相似性的片段描述符，这些描述符将在未来的工作中用于寻找生物电子等排体替代物。十七个与药物设计相关的常见有机片段作为“连接基团”，由两个端基封端。每个端基可以是12种可能基团中的一种：10个芳杂环、一个苯环或一个乙基。这使得能够对化学环境进行系统研究，连接基团内具有丰富的构象灵活性，总共涉及307个不同的原子。研究了五种不同水平的理论。这项工作为构建量子力学生物电子等排体片段数据库铺平了道路，对于该数据库而言，所存储片段性质的可转移性至关重要。
