Two-dimensional (2-D) similarity methods

PubChem subgraph fingerprints,

In 2-D similarity methods, structural similarity between two molecules is estimated by comparing their molecular fingerprints. 

targets

In substructure search, one provides an input substructure as a query to find molecules that contain the query substructure

Although each compound has up to 500 conformers (depending on the molecular size and flexibility),

PubChem homepage (http://pubchem.ncbi.nlm.nih.gov) PubChem Chemical Structure Search (https://pubchem.ncbi.nlm.nih.gov/search/search.cgi) PubChem Search (https://pubchem.ncbi.nlm.nih.gov/search/).

Shape-Tanimoto (ST): quantifies steric shape similarity between two conformers. Color-Tanimoto (CT): quantifies the overlap of functional groups between two conformers, such as hydrogen bond donors and acceptors, cations, anions, rings, and hydrophobes. Combo-Tanimoto (ComboT): the sum of ST and CT scores between two conformers.  It takes into account the shape similarity (ST) and functional group similarity (CT) simultaneously. 

The Structure Clustering tool

? [Note that a compound may have multiple EC50 values determined from different experiments (likely under different experimental conditions)

To perform an identity search for Cymbalta (CID 60835), go to the Chemical Structure Search pag

heat map-style layout,

the Structure Clustering tool and Structure-Activity Relationship (SAR) Analysis tool.

1.3. Substructure and superstructure search

As an alternative to 2-D similarity search, 3-D similarity search can also be performed using the “3D conformer” tab in PubChem Chemical Structure Search.  3-D similarity methods use the 3-D structures (that is, conformations) of molecules.  PubChem’s 3-D similarity method is based on the atom-centered Gaussian-shape comparison method by Grant and coworkers,9-12 implemented in the Rapid Overlay of Chemical Structures (ROCS).13,14  While the underlying mathematics of this approach is beyond the scope of this module, what this method essentially does is to find the “best” alignment of the 3-D structures of two molecules, which gives the maximized overlap between them.  The 3-D similarity method quantifies the 3-D molecular similarity using three metrics

wo-dimensional (2-D) similarity methods

However, molecular formula search implemented in some databases, including PubChem Chemical Structure Search, has an option to allow other elements in returned hits (e.g., C6H6O or C6H6N2O for the “C6H6” query).

The most common types of molecular fingerprints are structural keys, which encode structural information of a molecule into a binary string (that is, a string of 0’s and 1’s).  The position of each number in this string corresponds to a particular fragment.  If the molecule has a particular fragment, the corresponding bit position is set to 1, and otherwise to 0.  Note that there are many different ways to design molecular fingerprints, depending on what fragments are included in the fingerprint definition.  PubChem uses its own fingerprint called PubChem subgraph fingerprints.

PubChem provides two web-based tools that allow users to perform a cluster analysis of PubChem data:  the Structure Clustering tool and Structure-Activity Relationship (SAR) Analysis tool.

The Structure-Activity Relationship (SAR) Analysis tool

MMFF94s

Consist of only supported elements (H, C, N, O, F, Si, P, S, Cl, Br, and I).

Document Version HistoryV1.3 – 2009May01 – Updated introduction to describe how to identify the PubChem Substructure Fingerprint property in a PubChem Compound record. V1.2 – 2007Aug30 – Added section on decoding PubChem fingerprints. V1.1 – 2007Aug06 – Corrected and expanded documentation of bits with SMARTS patterns used. V1.0 – 2005Dec02 - Initial release.

1 SimilarityCoefficients

ELISA

The method is also used to quantify the degree of chirality of asymmetric molecules and to investigate the chirality of biphenyl and the amino acids.

ROCS is a fast shape comparison application, based on the idea that molecules have similar shape if their volumes overlay well and any volume mismatch is a measure of dissimilarity. It uses a smooth Gaussian function to represent the molecular volume [5], so it is possible to routinely minimize to the best global match.

Options Identical Structures Similar Compounds, score >= 95% Similar Compounds, score >= 90% Similar Compounds, score >= 80% Identical Structures Similar Structures with  same connectivity any tautomer same stereoisomer same isotopical labels same stereochemistry and isotopes non-conflicting stereochemistry same isotopes and non-conflicting stereoisomers   threshold >=  99% 98% 97% 96% 95% 93% 90% 85% 80% 70% 60%   Substructure Superstructure Substructure Superstructure match stereochemistry  Ignore Exact Relative Nonconflicting  and  Match isotopes Match charges Match tautomers Ringsystems not embedded Single/double bonds match aromatic bonds Chain bonds match ring bonds Strip hydrogen   Molecular Formula with  exact stoichiometry allow other element   Sort results by: Shape-then-featureFeature-then-shapeShape-and-featureConformer Id Output to: PubChem 3D Alignment ViewerNCBI EntrezTable Summary Time Limit(seconds):  unlimited 30 60 90 300 600 3,600      Result Limit: 10 50 100 500 1,000 10,000 100,000 2,000,000   Filters

The method provides good accuracy across a range of organic and drug-like molecules. The core parameterization was provided by high-quality quantum calculations, rather than experimental data, across ~500 test molecular systems. The method includes parameters for a wide range of atom types including the following common organic elements: C, H, N, O, F, Si, P, S, Cl, Br, and I. It also supports the following common ions: Fe+2, Fe+3, F-, Cl-, Br-, Li+, Na+, K+, Zn+2, Ca+2, Cu+1, Cu+2, and Mg+2. The Open Babel implementation should automatically perform atom typing and recognize these elements.

ST=VABVAA+VBB−VAB