PubChem3D: a new resource for scientists

By Evan E. Bolton, Jie Chen, Sunghwan Kim, Lianyi Han, Siqian He, Wenyao Shi, Vahan Simonyan, Yan Lindsay Sun, Paul A. Thiessen, Jiyao Wang and 3 more. 2011

179 citations recorded by the source corpus.

BackgroundPubChem is an open repository for small molecules and their experimental biological activity. PubChem integrates and provides search, retrieval, visualization, analysis, and programmatic access tools in an effort to maximize the utility of contributed information. There are many diverse chemical structures with similar biological efficacies against targets available in PubChem that are difficult to interrelate using traditional 2-D similarity methods. A new layer called PubChem3D is added to PubChem to assist in this analysis.DescriptionPubChem generates a 3-D conformer model description for 92.3% of all records in the PubChem Compound database (when considering the parent compound of salts). Each of these conformer models is sampled to remove redundancy, guaranteeing a minimum (non-hydrogen atom pair-wise) RMSD between conformers. A diverse conformer ordering gives a maximal description of the conformational diversity of a molecule when only a subset of available conformers is used. A pre-computed search per compound record gives immediate access to a set of 3-D similar compounds (called "Similar Conformers") in PubChem and their respective superpositions. Systematic augmentation of PubChem resources to include a 3-D layer provides users with new capabilities to search, subset, visualize, analyze, and download data.A series of retrospective studies help to demonstrate important connections between chemical structures and their biological function that are not obvious using 2-D similarity but are readily apparent by 3-D similarity.ConclusionsThe addition of PubChem3D to the existing contents of PubChem is a considerable achievement, given the scope, scale, and the fact that the resource is publicly accessible and free. With the ability to uncover latent structure-activity relationships of chemical structures, while complementing 2-D similarity analysis approaches, PubChem3D represents a new resource for scientists to exploit when exploring the biological annotations in PubChem.

Subfields: Computational Theory and Mathematics, Materials Chemistry, Spectroscopy

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Citations in the corpus

Effects of multiple conformers per compound upon 3-D similarity search and bioassay data analysis (2012, methodology): “In the case of PubChem3D, each 3-D conformer model consists of up to 500 conformers (with an average of 115 conformers) [11].”
PubChemRDF: towards the semantic annotation of PubChem compound and substance databases (2015, background): “D conformers which are pre-computed for more than 90% of the PubChem compound records [46].”
PubChem structure–activity relationship (SAR) clusters (2015, methodology): “In addition to the 2-D similarity measure using the PubChem fingerprint and Tanimoto equation, PubChem uses two 3-D similarity metrics: shape-Tanimoto (ST) [19, 21, 22, 25–28] and color-Tanimoto (CT) [19, 21, 22, 26].”
UCSF ChimeraX: Tools for structure building and analysis (2023, methodology): “The ChimeraX Build Structure tool (described in more detail below) allows fetching modeled small-molecule structures from web resources such as PubChem3D (Bolton et al., 2011) and the PDB Chemical Components Dictionary (Westbrook et al., 2015), making atom-by-atom modifications, and building peptide”
UCSF ChimeraX: Structure visualization for researchers, educators, and developers (2020, methodology): “Data can be opened from local files and/or fetched directly from online repositories or web services, including the Research Collaboratory for Structure Bioinformatics (RCSB) Protein DataBank 18 (PDB), Electron Microscopy Data Bank 21 (EMDB), PubChem3D, 22 and UniProt.”
PubChem3D: conformer ensemble accuracy (2013, methodology): “A diverse conformer ordering [10] gives a maximal description of the conformational space of a molecule when only a subset of available conformers is used.”