Reviewed by Susan Boyd, CompChem Solutions, UK
If you’ve ever tried to create protein structure-based pharmacophores from existing molecular modelling packages, you’ll know it’s not usually a fast process. LigandScout changes all that. This very simple but very powerful tool reduces the whole process to a few mouse clicks, and has the added advantage that the pharmacophores created this way can be directly exported into common pharmacophore format files, which can be directly imported into standard software packages.
LigandScout takes a macromolecular structure, containing a bound ligand (which can be a co-crystal structure or simply a ligand docked-in using a modelling package) and identifies the key features on the ligand which are interacting with points on the protein1. These, complete with a series of excluded volume features defining the shape of the active site, are automatically detected by the software and are merged into the pharmacophore.
Pharmacophores can also be created from ligands in the absence of a protein structure, but no excluded volumes are included in the output pharmacophore and the directionality of donor/acceptor groups is excluded where there may be ambiguity in positioning.
The software allows alignment of either a set of ligand molecules, or of a set of pharmacophores.Pharmacophores can be merged to create both all-encompassing consensus pharmacophores, containing all features of all input pharmacophores, or shared feature pharmacophores, which only extract the features (including volumes) that are common to all members of the input set of pharmacophores to allow identification of common binding modes. Pharmacophores can be manually edited if required.
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