Molecular Surface Point Environments for Virtual Screening and the Elucidation of Binding Patterns (MOLPRINT 3D)

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Abstract
A novel method (MOLPRINT 3D) for virtual screening and the elucidation of ligand−receptor binding patterns is introduced that is based on environments of molecular surface points. The descriptor uses points relative to the molecular coordinates, thus it is translationally and rotationally invariant. Due to its local nature, conformational variations cause only minor changes in the descriptor. If surface point environments are combined with the Tanimoto coefficient and applied to virtual screening, they achieve retrieval rates comparable to that of two-dimensional (2D) fingerprints. The identification of active structures with minimal 2D similarity (“scaffold hopping”) is facilitated. In combination with information-gain-based feature selection and a naïve Bayesian classifier, information from multiple molecules can be combined and classification performance can be improved. Selected features are consistent with experimentally determined binding patterns. Examples are given for angiotensin-converting enzyme inhibitors, 3-hydroxy-3-methylglutaryl−coenzyme A reductase inhibitors, and thromboxane A2 antagonists.