PubChem3D: a new resource for scientists

Abstract

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.

Computational allosteric ligand binding site identification on Ras proteins

“…There is a wealth of freely available data on small-molecule ligands in public databases such as ZINC [76] and PubChem [77]. These depositories of large numbers of drug-like small molecules provide ready-to-use, downloadable files of ligand libraries [63,77]. A focused library biased toward a given set of compounds can also be generated based on known high affinity binders via similarity searches and knowledge-based culling [63].…”

“…In short, HTVS requires a careful selection of a small-molecule ligand library [72], which involves among other things setting up criteria for molecular size, solubility, and cell permeability [73][74][75]. There is a wealth of freely available data on small-molecule ligands in public databases such as ZINC [76] and PubChem [77]. These depositories of large numbers of drug-like small molecules provide ready-to-use, downloadable files of ligand libraries [63,77].…”

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure

“…Although a close similarity between compounds can never guarantee an overlap in the mechanism of action, there is a strong correlation between the presence of certain structural subunits in a molecule and the eventual biological effect, which is a relationship that is often explored during the development of new pharmaceutical compounds. The Tanimoto coefficient [17] is a frequently used measure of chemical similarity and will be applied here to focus purely on the overlap in chemical properties of the compounds in the test data set.…”

Study of Contribution of Chemical and Physical Properties of Molecules towards Their Activities against Ebola Virus Using Data Mining Techniques

“…Conversions of chemical structural formats were done using Open Babel [28]. Molecular visualization was done using Pc3D Viewer from PubChem [29].…”