Sitnikov Gleb V, Zhokhova Nelly I, Ustynyuk Yury A, Varnek Alexandre, Baskin Igor I
A.N.Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, 119991, Moscow, Russia.
J Comput Aided Mol Des. 2015 Mar;29(3):233-47. doi: 10.1007/s10822-014-9818-z. Epub 2014 Dec 2.
A novel type of molecular fields, Continuous Indicator Fields (CIFs), is suggested to provide 3D structural description of molecules. The values of CIFs are calculated as the degree to which a point with given 3D coordinates belongs to an atom of a certain type. They can be used similarly to standard physicochemical fields for building 3D structure-activity models. One can build CIF-based 3D structure-activity models in the framework of the continuous molecular fields approach described earlier (J Comput-Aided Mol Des 27 (5):427-442, 2013) for the case of physicochemical molecular fields. CIFs are thought to complement and further extend traditional physicochemical fields. The models built with CIFs can be interpreted in terms of preferable and undesirable positions of certain types of atoms in space. This helps to understand which changes in chemical structure should be made in order to design a compound possessing desirable properties. We have demonstrated that CIFs can be considered as 3D analogues of 2D topological molecular fragments. The performance of this approach is demonstrated in structure-activity studies of thrombin inhibitors, multidentate N-heterocyclic ligands for Am(3+)/Eu(3+) separation, and coloring dyes.
一种新型的分子场，即连续指示场（CIFs），被提出来用于提供分子的三维结构描述。CIFs的值是根据具有给定三维坐标的点属于某一类型原子的程度来计算的。它们可以像标准物理化学场一样用于构建三维结构-活性模型。在前面描述的连续分子场方法（《计算机辅助分子设计杂志》27(5):427 - 442, 2013）的框架内，对于物理化学分子场的情况，可以构建基于CIFs的三维结构-活性模型。CIFs被认为是对传统物理化学场的补充和进一步扩展。用CIFs构建的模型可以根据某些类型原子在空间中的优选和非优选位置来解释。这有助于理解为了设计具有理想性质的化合物应该进行哪些化学结构上的改变。我们已经证明CIFs可以被视为二维拓扑分子片段的三维类似物。这种方法的性能在凝血酶抑制剂、用于镅(3 +)/铕(3 +)分离的多齿N - 杂环配体以及着色染料的结构-活性研究中得到了证明。
