A simple electrotopological index for quantitative structure-activity relationship correlation of physical properties wi
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A simple electrotopological index for quantitative structure-activity relationship correlation of physical properties with biomolecular activities Ian N. Weaver · Donald F. Weaver
Received: 21 August 2012 / Accepted: 3 January 2013 / Published online: 13 January 2013 © Springer Science+Business Media New York 2013
Abstract Quantitative structure-activity relationship (QSAR) studies constitute a process by which the physicochemical properties of a set of chemical structures are quantitatively correlated with a measurable, such as the concentration of a substance required to give a certain therapeutic drug response. 2D-QSAR studies start with 10– 20 analogues, ranging from biologically active to inactive; each analogue, regardless of bioactivity, is described by a series of descriptors. To further broaden the practical utility of these simple descriptors we have sought to identify hybrid indices which are trivial to calculate but which capture data from at least two categories of descriptors. An electrotopological descriptor, termed ETZ , which combines electronic information and molecular topology, has been devised and validated against a set of 25 anticonvulsant hydantoin molecules. This ETZ is based solely on atomic connectivity information obtained from the graph without explicit input from molecular geometry. Keywords Quantitative structure-activity relationship study · Descriptors · Topological index · Electrotopological index · Computer-aided drug design
Quantitative structure-activity relationship (QSAR) studies constitute a process by which the physicochemical properties of a defined set of chemical structures are
I. N. Weaver · D. F. Weaver (B) Departments of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada e-mail: [email protected] D. F. Weaver Departments of Chemistry, Dalhousie University, Halifax, NS, Canada D. F. Weaver Departments of Medicine (Neurology), Dalhousie University, Halifax, NS, Canada
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J Math Chem (2013) 51:811–816
quantitatively correlated with a rigorously defined measurable, such as the concentration of a substance required to give a certain biological response. QSAR is widely used during the optimization phase of drug design [1–7]. Over the past 30 years, QSAR has progressed from the simple regression equations of Hansch (1D-QSAR) to more modern 2D-QSAR [8–10]. Typically, 2D-QSAR studies start with 10–20 analogues, ranging from biologically active to inactive. Each analogue, regardless of bioactivity, is described by a series of descriptors which can be divided into four categories. [i] Geometric descriptors reflect dimensions such as bond lengths, bond angles and interatomic distances within the analogue series. [ii] Electronic descriptors represent properties such as atomic charge densities, molecular dipoles, and energy of the highest occupied molecular orbital. [iii] Topological descriptors encode aspects of molecular shape and branching and are frequently represented by graph theory indices. [iv] Physicochemical descriptors include values such as
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