GenProBiS: web server for mapping of sequence variants to protein binding sites

Abstract

Discovery of potentially deleterious sequence variants is important and has wide implications for research and generation of new hypotheses in human and veterinary medicine, and drug discovery. The GenProBiS web server maps sequence variants to protein structures from the Protein Data Bank (PDB), and further to protein–protein, protein–nucleic acid, protein–compound, and protein–metal ion binding sites. The concept of a protein–compound binding site is understood in the broadest sense, which includes glycosylation and other post-translational modification sites. Binding sites were defined by local structural comparisons of whole protein structures using the Protein Binding Sites (ProBiS) algorithm and transposition of ligands from the similar binding sites found to the query protein using the ProBiS-ligands approach with new improvements introduced in GenProBiS. Binding site surfaces were generated as three-dimensional grids encompassing the space occupied by predicted ligands. The server allows intuitive visual exploration of comprehensively mapped variants, such as human somatic mis-sense mutations related to cancer and non-synonymous single nucleotide polymorphisms from 21 species, within the predicted binding sites regions for about 80 000 PDB protein structures using fast WebGL graphics. The GenProBiS web server is open and free to all users at http://genprobis.insilab.org.

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

“…ProBiS local structural alignment algorithm, was used to obtain superimposed protein‐ion binding sites. The non‐redundant set of 100 % sequence identical protein chains (∼70,000 protein chains) downloaded from the PDB (August, 2017) was compared all‐against‐all resulting in about 4,9 billion local pairwise alignments.…”

“…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.…”

Deep node ranking for neuro‐symbolic structural node embedding and classification

“…The ions data set is based on the recently introduced protein-ion binding site similarity network. 47 The network was constructed by structural alignment using the ProBiS family of algorithms [48][49][50] where all known protein-ion binding sites were considered. The obtained network was pruned for structural redundancy as described in Škrlj et al 47 Each node corresponds to one of 12 possible ions, and each weighted connection corresponds to the ion-binding site similarity between the two considered binding sites.…”

Rise of Systems Glycobiology and Personalized Glycomedicine: Why and How to Integrate Glycomics with Multiomics Science?

“…An estimation of the number of these interactions is an important study question for future studies. Bioinformatics tool GenProBiS (Konc et al, 2017), for example, enables protein-protein, protein-nucleic acid, and protein-compound binding site analysis, including glycosylation and other post-translational modification sites. Moreover, it maps sequence variants to protein structures.…”