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.

New Structural Descriptors of Molecules on the Basis of Symbiosis of the Informational Field Model and Simplex Representation of Molecular Structure

“…In the SiRMS all atoms in simplex can be differentiated on the base of the different descriptive (atom type) and physical-chemical characteristics (atom charge, lipophilicity, etc ) [4].…”

Consensus QSAR Modeling of Phosphor‐Containing Chiral AChE Inhibitors

“…In the frameworks of SiRMS any molecule can be represented as the system of different simplexes (tetratomic fragments of fixed composition, structure, chirality and symmetry) [28,29,33,39]. SiRMS has been well-described earlier [13,29,33], therefore only 3D and novel 2.5D and double 2.5D protocols (see description below) used for current research will be presented in this article.…”

“…According to multihierarchical HiT QSAR nature [29], the SD of 3D and 2D (number of simplexes of fixed composition and topology) levels have been used for 3D QSAR analysis. It is necessary to note that at the 2D level along with SD the other structural parameters corresponding to molecular fragments of different length (1 -3 atoms in the current work) can be also used.…”

“…The detailed description of HiT QSAR can be found in the reference [29]. In the frameworks of SiRMS any molecule can be represented as the system of different simplexes (tetratomic fragments of fixed composition, structure, chirality and symmetry) [28,29,33,39].…”

“…HiT QSAR [27,29] allows carrying out QSAR task on various (1D -4D) levels of molecular structure representation as it was proved by numerous studies [9,12,13,30]. Thus, HiT QSAR has been selected as a main research tool used in this work.…”