Harmonization of the R-group query search and Markush search
Structures with R-groups in more detailR-group structures consist of a scaffold, R-group definitions, and R-logic conditions.
R-group structure as query structureWhen using this R-group structure as query structure, we are not only matching the scaffold and the ligands defined in R-group definitions during the search process, but also the R-logic conditions. “R1 2” defines the occurrence of R1 substituents; exactly two R1 atom of the scaffold must be substituted with OH and/or OMe. “restH” defines that no other substituent can be present on carbon atoms where R1 atom is attached on the scaffold (restH) except hydrogen. “R2 1” defines the occurrence of R2; exactly one R2 must be susbtituted with F or Cl or Br. In the case the user doesn’t specify R-logic conditions, the default R-logic condition is taken into account during the search. Until version 6.2, the default R-logic occurrence value was: >0.
R-group structure with former default R-logic:at least one R1 and at least one R2 is substituted with the given ligands.
Markush structures for representing large number of specific chemical structuresBesides query structures, R-group structures are used in Markush structures for representing large numbers of specific chemical structures in one complex Markush structure or library. In Markush structures, the occurrence of the R atoms is definitely determined. A Markush structure represents all those specific structures in which all R-atoms are substituted according to their definitions. all the three R1 and both R2 are substituted with the given ligands.
Harmonizing both behavioursAs you can see, structures with R-groups are interpreted differently depending on whether it is a query or a Markush structure. To eliminate this discrepancy we changed the default value of occurrence range in R-logic to ALL (*), because chemists regard R-group structures as they are used in Markush structures.
New default R-logic occurrence value ALLSince version 6.2.0, the new R-logic default value is * (meaning all). all the three R1 and both R2 are substituted with the given ligands.
Possible problem casesWhen R-group structures are used as query structures
R-group structures saved in mrv format do not contain explicitly the old default '>0' information, and when you open them with JChem/Marvin 6.2.0, the new default occurrence value '*' will be present. For restoring the search behavior (e.g., expected hits/no-hits with former versions) the '*' (unspecified) must be changed to '>0' .
MarvinSketch / Structure>Attribute>R-logic
There is no need of any modification in case of RGfile format because this format explicitly saves the ’>0’ information.
When R-group structures are stored in or imported to Markush library database tables
If your database tables already contain R-group structures imported from RGfiles or you would like to import structures from RGfiles having the old default value, ’>0’ explicitly stored, since JChem version 6.2.0, this old default ’>0’ occurrence range data will be treated as the new default occurrence range ’*’.If the R-group structures were originally imported from mrv file, there is no need for any special action. As previously mentioned R-group structures saved in mrv format do not explicitly contain the old default '>0' information, so the new default occurrence value '*' will be present.