Generalized molecular descriptors derived from event-based discrete derivative

Abstract

In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22-24), an unique event, named connected subgraphs, (based on the Kier-Hall’s subgraphs) was systematically employed for the computation of the matrix F. The present report is a generalization of this notion, in which eleven additional events are introduced, classified in three categories, namely, topological (terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach’s subgraphs), fingerprints (MACCs, E-state and substructure fingerprints) and atomic contributions (Ghose and Crippen atom-types for hydrophobicity and refractivity) for F generation. The events are intended to capture diverse information by the generation or search of different kinds of substructures from the graph representation of a molecule. The discrete derivative over duplex atom relations are calculated for each event, and the resulting derivatives, local vertex invariants (LOVIs) are finally obtained. These LOVIs are subsequently employed as the basis for the calculation of global and local indices over groups of atoms (heteroatoms, halogens, methyl carbons, etc.), by using norms, means, statistics and classical algorithms as aggregator (fusion) operators. These indices were implemented in our house software DIVATI (Derivative Type Indices, a new module of TOMOCOMDCARDD system). DIVATI provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http: //www.tomocomd.com. Factor analysis shows that the presented events are rather orthogonal and collect diverse information about the chemical structure. Finally, QSPR models were built to describe the logP and logK of 34 furylethylenes derivatives using the eleven events. Generally, the equations obtained according to these events showed high correlations, with the Sach’s sub-graphs and Multiplicity events showing the best behavior in the description of logK (Q2LOO value of 99.06%) and logP (Q2LOO value of 98.1%), respectively. These results show that these new eventbased indices constitute a powerful approach for chemoinformatics studies. © 2016 Bentham Science Publishers.