Use of Compound Structural Descriptors for Increasing the Efficiency of QSAR Study

Abstract

A new concept of describing the dependence of the mutagenic activity of a chemical substance on its structure (QSAR analysis) is presented. It involves compound descriptors, which are combinations of unrelated fragments of molecular structure. Software has been developed to generate various structural fragments of molecules and their combinations (ensembles) and select compound descriptors of statistical significance for the biological activity of a chemical. By examples of univocal compound descriptors consisting of two structural fragments and present only in active or only in inactive compounds, it has been shown that the efficiency of QSAR study can be increased fourfold or more. The approach has been applied to a set of 105 compounds whose mutagenic effect on rodent germline cells is known.

Fragment Descriptors in SAR/QSAR/QSPR Studies, Molecular Similarity Analysis and in Virtual Screening

“…into logical expressions instead of nonlinear terms for connected fragments. Tarasov et al 222 have shown that the compound structural descriptors defined as combinations of unrelated fragments improve significantly the efficiency of mutagenicity predictions. Implicitly, disconnected fragments, as conjugations of binary (logical) connected fragment descriptors, were used to build probabilistic SAR models for some biological activities (see ref.…”