Comparison of Shape-Matching and Docking as Virtual Screening Tools

OpenEye Scientific Software, Santa Fe, New Mexico 87507, USA.
Journal of Medicinal Chemistry (Impact Factor: 5.45). 02/2007; 50(1):74-82. DOI: 10.1021/jm0603365
Source: PubMed


Ligand docking is a widely used approach in virtual screening. In recent years a large number of publications have appeared in which docking tools are compared and evaluated for their effectiveness in virtual screening against a wide variety of protein targets. These studies have shown that the effectiveness of docking in virtual screening is highly variable due to a large number of possible confounding factors. Another class of method that has shown promise in virtual screening is the shape-based, ligand-centric approach. Several direct comparisons of docking with the shape-based tool ROCS have been conducted using data sets from some of these recent docking publications. The results show that a shape-based, ligand-centric approach is more consistent than, and often superior to, the protein-centric approach taken by docking.

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    • "The goal of ligand–protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Virtual screening on the basis of molecular descriptors and physicochemical properties of active ligands has great usefulness in finding hits and leads through library enrichment for screening (28), a strategy that is also well-used for reducing and enriching the library of ligands for molecular docking; there are recent reports that ligand shape-matching does as well as, if not better than, docking (29). "
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    Iranian journal of pharmaceutical research (IJPR) 03/2014; 13(1):49-65. · 1.07 Impact Factor
    • "Other methods are based on the assumption that molecules with a similar shape behave similar. These shape-based methods compare the volume of molecules and have been applied successfully in virtual screening and clustering [16] [17]. Molecular scaffolds offer an alternative way to describe molecular structures in a way that is particularly close to how a chemist sees a molecule. "
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    Biochimica et Biophysica Acta 05/2013; 1844(1). DOI:10.1016/j.bbapap.2013.05.010 · 4.66 Impact Factor
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    • "Because ROCS uses atom-centered Gaussian functions to describe the molecular shape [19,20], it can perform a rapid shape superposition without a considerable loss of accuracy, compared to when the hard-sphere volumes is employed. In recent studies [15,57], ROCS was shown to be comparable with, and often better than, structure-based approaches in virtual screening, both in terms of overall performance and consistency [17]. "
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