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PDBspheres - a method for finding 3D similarities in local regions in proteins

Zemla, A.; Allen, J. E.; Kirshner, D.; Lightstone, F. C.

2022-05-14 bioinformatics
10.1101/2022.01.04.474934 bioRxiv
Show abstract

We present a structure-based method for finding and evaluating structural similarities in protein regions relevant to ligand binding. PDBspheres comprises an exhaustive library of protein structure regions ("spheres") adjacent to complexed ligands derived from the Protein Data Bank (PDB), along with methods to find and evaluate structural matches between a protein of interest and spheres in the library. PDBspheres uses the LGA structure alignment algorithm as the main engine for detecting structure similarities between the protein of interest and template spheres from the library, which currently contains more than 2 million spheres. To assess confidence in structural matches an all-atom-based similarity metric takes sidechain placement into account. Here, we describe the PDBspheres method, demonstrate its ability to detect and characterize binding sites in protein structures, show how PDBspheres - a strictly structure-based method - performs on a curated dataset of 2,528 ligand-bound and ligand-free crystal structures, and use PDBspheres to cluster pockets and assess structural similarities among protein binding sites of 4,876 structures in the "refined set" of the PDBbind 2019 dataset.

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