Shapelets: Possibilities and limitations of shape‐based virtual screening

Complementarity of molecular surfaces is crucial for molecular recognition. A method for representation of molecular shape is presented. We decompose the molecular surface into commensurate patches with defined shape by fitting hyperbolical paraboloids onto a triangulated isosurface of the Gaussian model of a molecule. As a result of this decomposition we obtain a 3D graph representation of the molecular shape, which can be used for complete and partial shape matching and isosteric group searching. To point out the possibilities and limitations of shape‐only models, we challenged our method by three scenarios in a virtual screening contest: rigid body alignment, consensus shape filtering, and target‐specific screening. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

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