ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites

Abstract

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands.

Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme

“…1, E and F). Additionally, ProBis structural alignment (26,27) identified equivalent motifs involving residues Ile-932, Leu-934, Asn-936, and Lys-939 within the catalytic site and the corresponding Leu-687, Leu-690, Asn-691, and Arg-694 residues in the allosteric site (Table 1). Thus, despite differences in the overall topology, the catalytic and allosteric sites on SOS1 share some elements of structural similarity.…”

Insights from Ion Binding Site Network Analysis into Evolution and Functions of Proteins

“…The Protein Data Bank (PDB) is the largest database of experimental protein structures, which in 2017 includes more than 130,000 entries. This large population of known structures enabled the development of ion binding site prediction tools originating from the fields of information theory, machine learning,, graph theory and molecular dynamics simulations . The PDB‐wide protein‐ion interaction predictions offer a possibility to study ion binding sites at the global network level.…”

Discovery of Mycobacterium tuberculosis InhA Inhibitors by Binding Sites Comparison and Ligands Prediction

“…ProBiS plugin, freely available on our server at http://insilab.org/probis-plugin, is an extension of our earlier ProBiS-ligands approach 28 available at http://probis.cmm.ki.si that predicts protein ligands by searching for structurally similar binding sites and transposition of ligands between these sites. Major improvements in the ProBiS plugin over the earlier approach include:

ProBiS plugin enables prediction of small molecule ligands and binding sites for all ~290000 protein chains in the PDB, while the ProBiS-ligands approach only enabled prediction of ligands for the 42000 protein chains in the 95% nonredundant PDB.

The plugin calculates three-dimensional grid models of binding sites that define the size and the shape of the predicted binding sites.

The new database of binding site comparisons is focused on small ligand binding sites only, while the database used in ProBiS-ligands considered whole protein surfaces.

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