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.
