Abstract
BackgroundMeasures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Molecular similarity has been measured by a variety of methods including molecular descriptor based similarity, common molecular fragments, graph matching and 3D methods such as shape matching. Similarity measures are widespread in practice and have proven to be useful in drug discovery. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule.ResultsA new molecular descriptor based on partial charges is proposed. It uses the autocorrelation function and linear binning to encode all atoms of a molecule into two rotation-translation invariant vectors. Combined with a scoring function, the descriptor allows to rank-order a database of compounds versus a query molecule. The proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and released in open source. Extensive retrospective ligand-based virtual screening experiments were performed and other methods were compared with in order to validate the method and associated protocol.ConclusionsWhile it is a simple method, it performed remarkably well in experiments. At an average speed of 1649 molecules per second, it reached an average median area under the curve of 0.81 on 40 different targets; hence validating the proposed protocol and implementation.
Highlights
Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics
Various molecular similarity measures have been developed [9]. Those include measures based on molecular descriptors [10], measures based on molecular fragments and measures based on graph matching
Due to our recent study on the electrostatic similarity of small molecules with binding proteins [20], we were interested in the challenge of looking for active compounds while only exploiting the information contained in atomic coordinates and partial charges of a molecule
Summary
Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule. Molecules sharing similar electrostatics and shape are expected to bind to the same receptor This principle has been used in ligand-based virtual screening to look for small molecules similar to known inhibitors and natural substrates [16,17,18,19]. Due to our recent study on the electrostatic similarity of small molecules with binding proteins [20], we were interested in the challenge of looking for active compounds while only exploiting the information contained in atomic coordinates and partial charges of a molecule
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