A fast topological analysis algorithm for large-scale similarity evaluations of ligands and binding pockets

MOTIVATION: With the rapid increase of the structural data of biomolecular complexes, novel structural analysis methods have to be devised with high-throughput capacity to handle immense data input and to construct massive networks at the minimal computational cost. Moreover, novel methods should be capable of handling a broad range of molecular structural sizes and chemical natures, cognisant of the conformational and electrostatic bases of molecular recognition, and sufficiently accurate to enable contextually relevant biological inferences. RESULTS: A novel molecular topology comparison method was developed and tested. The method was tested for both ligand and binding pocket similarity analyses and a PDB-wide ligand topological similarity map was computed. CONCLUSION: The unprecedentedly wide scope of ligand definition and large-scale topological similarity mapping can provide very robust tools, of performance unmatched by the present alignment-based methods. The method remarkably shows potential for application for scaffold hopping purposes. It also opens new frontiers in the areas of ligand-mediated protein connectivity, ligand-based molecular phylogeny, target fishing, and off-target predictions. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13321-015-0091-5) contains supplementary material, which is available to authorized users.