Kuz'min Victor E, Artemenko Anatoly G, Polischuk Pavel G, Muratov Eugene N, Hromov Alexander I, Liahovskiy Anatoly V, Andronati Sergey A, Makan Svetlana Yu
A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences, 7 Ukraine, Lustdorfskaya doroga 86, Odessa, 65080, Ukraine.
J Mol Model. 2005 Nov;11(6):457-67. doi: 10.1007/s00894-005-0237-x. Epub 2005 Oct 20.
In this work, a hierarchic system of QSAR models from 1D to 4D is considered on the basis of the simplex representation of molecular structure (SiRMS). The essence of this system is that the QSAR problem is solved sequentially in a series of the improved models of the description of molecular structure. Thus, at each subsequent stage of a hierarchic system, the QSAR problem is not solved ab ovo, but rather the information obtained from the previous step is used. Actually, we deal with a system of solutions defined more exactly. In the SiRMS approach, a molecule is represented as a system of different simplex descriptors (tetratomic fragments with fixed composition, structure, chirality and symmetry). The level of simplex-descriptor detail increases consecutively from 1D to 4D representations of molecular structure. It enables us to determine the fragments of structure that promote or interfere with the given biological activity easily. Molecular design of compounds with a given level of activity is possible on the basis of SiRMS. The efficiency of the method is demonstrated for the example of the analysis of substituted piperazines affinity for the 5-HT1A receptor.
在这项工作中，基于分子结构的单纯形表示法（SiRMS），考虑了一个从1D到4D的QSAR模型层次系统。该系统的本质是，在一系列改进的分子结构描述模型中依次解决QSAR问题。因此，在层次系统的每个后续阶段，不是从头开始解决QSAR问题，而是利用上一步获得的信息。实际上，我们处理的是一个定义更精确的解决方案系统。在SiRMS方法中，分子被表示为不同单纯形描述符的系统（具有固定组成、结构、手性和对称性的四原子片段）。单纯形描述符的细节水平从分子结构的1D表示到4D表示依次增加。这使我们能够轻松确定促进或干扰给定生物活性的结构片段。基于SiRMS可以进行具有给定活性水平的化合物的分子设计。以分析取代哌嗪对5-HT1A受体的亲和力为例，证明了该方法的有效性。
