Proteins form a complex network of physical interactions. Understanding these interactions on the scale of the structural interactome is an open problem that, if solved, could provide insights into the development of various diseases and protein function on the system level. The global protein-ligand interaction network, in which ligands are other proteins, compounds, ions, cofactors, nucleic acids or conserved water molecules, will be presented. Each node in the network represents a protein or a ligand and an edge represents a physical protein-ligand interaction. Two types of interactions are considered: those that directly correspond to a determined protein ligand complex in the PDB, and those that are predicted to occur based on the determined binding site similarities using our previously developed ProBiS algorithm. The network includes many layers of biological annotations, from genomic to proteomic to structural and consist of more than 100,000 protein nodes, and presumably millions of non-protein nodes representing other ligand types. To explore this network in an intuitive manner, we develop ProBiS-ATLAS, a graphical web-based atlas that enable the network to be viewed globally, similar to the Earth in Google Maps, or locally by focusing on a layer of interactions around a single protein. This atlas enable finding interactions between protein structures, predicting ligand selectivity and binding, and observing effects of conserved waters and sequence variants on ligand binding. This work provides the scientific community with a free, versatile server readily usable from the web by researchers and clinicians to discover molecules binding to proteins. ProBiS-ATLAS can be used in precision medicine for prediction of drug response.

Protein interaction atlas for prediction of genetic variations involved in drug interactions and disease development

2019 Spring National Meeting

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