FAF-Drugs4 and FAF-QED flow-chart

  • Both services share a Data Curation procedure (which could be also applied using the Bank Cleaner online tool) prior data calculations and filtering steps. That step gather a removal of large coumpounds, inorganics, mixtures, counterions, empty structures, and 211 salts known to be employed in medicinal chemistry. Then, the standardization procedure is performed, after a neutralization step, using the ChemAxon Standardizer [22] Academic package which involves a ring aromatization protocol and in-house SMARTS depicting patterns for key chemical functions (amine, nitro, carboxylic acid, phosphonamide, amide, sulfonamide, phosphonate and sulfonate). Duplicates are detected using internal CANSMILES defintions (Pybel) for each normalized compounds. During this step, stereochemistry is considered in order to keep stereoisomers. Note that user can employ the Bank Formatter service in order to process a corrected input SDF file (single or multiple) with standard format needed for FAFDrugs. One can also use the Filter Editor service to design a tuned physchem filter applied in FAF-Drugs4. Then, for both services, input file is divided in sub-libraries and managed by as many subprocesses as subdivisions of this file has been prior created.

  • If user run FAF-Drugs4, physchem descriptors are computed using OpenBabel and ChemAxon. In order to properly compute protonation-dependent descriptors (HBA, HBD, charges...), a benchmarked in-house procedure employing ChemAxon [22] cxcalc library at physiological pH is applied dynamically during calculations (also applied for FAF-QED). Toxicophores and interferents SMARTS definitions were refined for 137 structural alerts and 515 PAINS. Depending of the filtering ranges, Accepted, Intermediate or Rejected files are written associated with all their csv results files

  • If user run FAF-QED, physchem descriptors and alerts are computed as FAF-Drugs4 and a csv file offering descriptors values and QED estimations are written.

  • When the entire process is done, all results and graphical reports are proposed on the Mobyle RPBS Portal and available to be download.