Hierarchic system of QSAR models (1D–4D) on the base of simplex representation of molecular structure

Abstract

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.