A template can evolve. When the structure is big enough, it is best t…

…o use the previously minimised structure as a starting point, instead of always regenerating the entire set of stacked R-groups. This leads to many more "wrong conformers". By setting a template to be the previously minimised structure, we are decreasing the size of the search space for the next R-group.

fegrow/package.py

@@ -160,15 +160,9 @@ def merge_R_group(scaffold, RGroup, replace_index):
         merged.RemoveConformer(c.GetId())
 
     # bookkeeping about scaffolding
-    # if the molecule was previously merged
-    if hasattr(scaffold, "template") and scaffold.template is not None:
-        # mol already had a connected e.g. a linker, therefore we use the area without the linker
-        template = scaffold.template
-    else:
-        # prepare the template
-        etemp = Chem.EditableMol(scaffold)
-        etemp.RemoveAtom(atom_to_replace.GetIdx())
-        template = etemp.GetMol()
+    etemp = Chem.EditableMol(scaffold)
+    etemp.RemoveAtom(atom_to_replace.GetIdx())
+    template = etemp.GetMol()
 
     with_template = RMol(merged)
     with_template._save_template(template)