In silico Drug Design: some concepts & tools - Bioinformatics: Ligand binding pockets
Bioinformatics : Ligand binding pockets
To design a compound, if you know the target and if you have a 3D structure for this target, it can be critical to identify likely binding pockets at the surface of this target (see for example our review Perot et al., DDT 2010), to score these pockets, to compare pockets from you target with databases of pockets... Many in silico tools have been developed (over 100) and below, I just provide some examples (NB: always think about checking the quality of the protein structure first (eg, with the VHELIBS application or online with MotiveValidator)).
Many computational methods are available to find pockets on protein surface. Two main types of tools were developed: those based on evolutionary algorithms and those that use structure-based algorithms. This last category can be subdivided in geometry- and energy-based algorithms (probe mapping methods and docking of fragments and compounds)...These approaches can find pockets and some also try to compute a druggability score (here meaning able to bind a low molecular weight drug-like compound). These tools work in general on static protein structures others that try to take into account flexibility... Some tools are more appropriate for the detection of binding pockets at protein-protein interfaces...where the pockets are usually different from pockets seen in enzyme, GPCRs and ion channels. Some tools are used to compare binding pockets, like for instance for compound repositioning
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