Adding open spectral data to MassBank and PubChem using open source tools to support non-targeted exposomics of mixtures.

The term "exposome" is defined as a comprehensive study of life-course environmental exposures and the associated biological responses. Humans are exposed to many different chemicals, which can pose a major threat to the well-being of humanity. Targeted or non-targeted mass spectrometry techniques are widely used to identify and characterize various environmental stressors when linking exposures to human health.

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry.

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.

PubChem in 2021: new data content and improved web interfaces.

PubChem (https://pubchem.ncbi.nlm.

PubChem 2019 update: improved access to chemical data.

PubChem (https://pubchem.ncbi.nlm.

Finding Potential Multitarget Ligands Using PubChem.

PubChem ( https://pubchem.ncbi.nlm.

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows.

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows.

PubChem BioAssay: 2017 update.

PubChem's BioAssay database (https://pubchem.ncbi.nlm.

Literature information in PubChem: associations between PubChem records and scientific articles.

Background: PubChem is an open archive consisting of a set of three primary public databases (BioAssay, Compound, and Substance). It contains information on a broad range of chemical entities, including small molecules, lipids, carbohydrates, and (chemically modified) amino acid and nucleic acid sequences (including siRNA and miRNA). Currently (as of Nov.

Balancing Protein Stability and Activity in Cancer: A New Approach for Identifying Driver Mutations Affecting CBL Ubiquitin Ligase Activation.

Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved, depicting the protein at different stages of its activation cycle and thus providing mechanistic insight underlying how stability-activity tradeoffs in cancer-related proteins-may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity.

PubChem Substance and Compound databases.

PubChem (https://pubchem.ncbi.nlm.

Structural Perspectives on the Evolutionary Expansion of Unique Protein-Protein Binding Sites.

Structures of protein complexes provide atomistic insights into protein interactions. Human proteins represent a quarter of all structures in the Protein Data Bank; however, available protein complexes cover less than 10% of the human proteome. Although it is theoretically possible to infer interactions in human proteins based on structures of homologous protein complexes, it is still unclear to what extent protein interactions and binding sites are conserved, and whether protein complexes from remotely related species can be used to infer interactions and binding sites.

Coverage of protein domain families with structural protein-protein interactions: current progress and future trends.

Protein interactions have evolved into highly precise and regulated networks adding an immense layer of complexity to cellular systems. The most accurate atomistic description of protein binding sites can be obtained directly from structures of protein complexes. The availability of structurally characterized protein interfaces significantly improves our understanding of interactomes, and the progress in structural characterization of protein-protein interactions (PPIs) can be measured by calculating the structural coverage of protein domain families.

PubChem BioAssay: 2014 update.

PubChem's BioAssay database (http://pubchem.ncbi.nlm.

Cancer missense mutations alter binding properties of proteins and their interaction networks.

Many studies have shown that missense mutations might play an important role in carcinogenesis. However, the extent to which cancer mutations might affect biomolecular interactions remains unclear. Here, we map glioblastoma missense mutations on the human protein interactome, model the structures of affected protein complexes and decipher the effect of mutations on protein-protein, protein-nucleic acid and protein-ion binding interfaces.

Mutations in DNA-binding loop of NFAT5 transcription factor produce unique outcomes on protein-DNA binding and dynamics.

The nuclear factor of activated T cells 5 (NFAT5 or TonEBP) is a Rel family transcriptional activator and is activated by hypertonic conditions. Several studies point to a possible connection between nuclear translocation and DNA binding; however, the mechanism of NFAT5 nuclear translocation and the effect of DNA binding on retaining NFAT5 in the nucleus are largely unknown. Recent experiments showed that different mutations introduced in the DNA-binding loop and dimerization interface were important for DNA binding and some of them decreased the nuclear-cytoplasm ratio of NFAT5.

Large-scale mapping of human protein interactome using structural complexes.

Although the identification of protein interactions by high-throughput (HTP) methods progresses at a fast pace, 'interactome' data sets still suffer from high rates of false positives and low coverage. To map the human protein interactome, we describe a new framework that uses experimental evidence on structural complexes, the atomic details of binding interfaces and evolutionary conservation. The structurally inferred interaction network is highly modular and more functionally coherent compared with experimental interaction networks derived from multiple literature citations.

PubChem's BioAssay Database.

PubChem (http://pubchem.ncbi.nlm.

IBIS (Inferred Biomolecular Interaction Server) reports, predicts and integrates multiple types of conserved interactions for proteins.

We have recently developed the Inferred Biomolecular Interaction Server (IBIS) and database, which reports, predicts and integrates different types of interaction partners and locations of binding sites in proteins based on the analysis of homologous structural complexes. Here, we highlight several new IBIS features and options. The server's webpage is now redesigned to allow users easier access to data for different interaction types.

Intrinsic protein disorder in human pathways.

We analyze human-specific KEGG pathways trying to understand the functional role of intrinsic disorder in proteins. Pathways provide a comprehensive picture of biological processes and allow better understanding of a protein's function within the specific context of its surroundings. Our study pinpoints a few specific pathways significantly enriched in disorder-containing proteins and identifies the role of these proteins within the framework of pathway relationships.

Knowledge-based annotation of small molecule binding sites in proteins.

Background: The study of protein-small molecule interactions is vital for understanding protein function and for practical applications in drug discovery. To benefit from the rapidly increasing structural data, it is essential to improve the tools that enable large scale binding site prediction with greater emphasis on their biological validity.

Results: We have developed a new method for the annotation of protein-small molecule binding sites, using inference by homology, which allows us to extend annotation onto protein sequences without experimental data available.

An overview of the PubChem BioAssay resource.

The PubChem BioAssay database (http://pubchem.ncbi.nlm.

ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder.

Most of the proteins in a cell assemble into complexes to carry out their function. In this work, we have created a new database (named ComSin) of protein structures in bound (complex) and unbound (single) states to provide a researcher with exhaustive information on structures of the same or homologous proteins in bound and unbound states. From the complete Protein Data Bank (PDB), we selected 24 910 pairs of protein structures in bound and unbound states, and identified regions of intrinsic disorder.

Evolution of protein binding modes in homooligomers.

The evolution of protein interactions cannot be deciphered without a detailed analysis of interaction interfaces and binding modes. We performed a large-scale study of protein homooligomers in terms of their symmetry, interface sizes, and conservation of binding modes. We also focused specifically on the evolution of protein binding modes from nine families of homooligomers and mapped 60 different binding modes and oligomerization states onto the phylogenetic trees of these families.