To confirm the activity of an initial small molecule "hit compound" from an activity screening, one needs to probe the structure-activity relationships (SAR) by testing close analogs.
The open access multi-fingerprint browser presented here, enables to rapidly identify such close analogs among commercially available compounds in the ZINC database (> 13 million molecules). The browser retrieves nearest neighbors in multi-dimensional chemical spaces defined by four different fingerprints (fingerprint = a vector composed of several numerical descriptors of molecular structure and properties), each of which represents relevant structural and pharmacophoric features in a different way: sFP (substructure fingerprint), ECFP4 (Extended connectivity fingerprint), MQN (Molecular Quantum Numbers) and SMIfp (SMILES fingerprint). Distances are calculated using the city-block distance (CBD), a similarity measure which performs as well as Tanimoto similarity but is much faster to compute.
The list of up to 1000 nearest neighbors of any query molecule are retrieved by the browser and can then be clustered to produce a focused list of analogs with likely similar bioactivity to be considered for experimental evaluation.
ZINC is an open-access database of commercially available small organic molecules for drug discovery, currently > 13 millions compounds. ZINC is provided by the Shoichet Laboratory in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF). For download and more information please visit https://docking.org/
Group of Prof. Jean-Louis Reymond
Dept. of Chemistry and Biochemistry