Building a molecule from fragments can save time, but it also creates a familiar problem: a fragment may land in an awkward orientation, overlap nearby atoms, or produce a connection that is chemically implausible. Adjusting the structure by trial and error can be frustrating—especially when you are still assembling it.
SAMSON’s Add editor can help manage these issues during construction. The workflow below shows how to prepare its options, connect fragments, and use orientation and minimization tools to refine the result. The examples use phenol and bisphenol A (BPA), but the same ideas apply to other fragment-based builds.
Set up before placing fragments
First, open Preferences > Editors > Add. Consider enabling the options that match your workflow:
- Adjust hydrogens when adding fragments adjusts hydrogens when adding or linking atoms and fragments, changing bond order, or changing formal charge, based on valences.
- Automatically orient fragments on substitution attempts to position a fragment so its atoms do not overlap with the existing molecule.
- Merge neighboring atoms merges sufficiently close atoms along with the substitution atoms when connecting a fragment.
- Prevent unexpected substitutions marks acceptable operations in green and forbidden ones in red.
These settings are aids, not a replacement for checking the structure. If a proposed operation is marked red, pause and inspect the attachment point rather than assuming the placement is suitable. You can control whether the substitution recommendations are enforced in Preferences.
Choose the attachment point deliberately
Activate the Add editor and choose a fragment in the Asset Browser. For fragments you have already built, select the relevant part of the structure, right-click, and choose Use selection to build. This turns the selection into a building fragment.
Before connecting a fragment, decide which atom should attach to the existing molecule. To change the substitution atom in a fragment, hold Ctrl on Windows/Linux or Cmd on macOS and choose the desired atom in the fragment. This small step matters: the wrong substitution atom can put the rest of the fragment in an unintended position, even if the connection itself is made successfully.
When building with the Add editor, you can connect by substituting an atom or by creating a bond. To substitute, move the fragment over the atom you want to replace and click. To create a bond, press and hold on the atom to attach to, move the cursor away to a bond-like distance, and release. The editor uses covalent radii when positioning added atoms or fragments.
Use orientation as a preview, not a final verdict
Automatic orientation can help avoid overlaps during substitution, but it is still useful to inspect the result. In the BPA example, a propane backbone is built first; the phenol asset is then selected, its substitution atom is changed to the desired carbon, and two hydrogens on the central carbon are substituted with phenol fragments. Watch the preview as you move the fragment over each attachment point. If the orientation is not what you want, you can rotate the fragment by holding Shift and right-clicking.
For a closer look at a placement after adding it, the Local Move Editor (shortcut M) lets you choose a pivot atom and rotate the selected fragment with its controls. Clicking a bond with this editor selects the shortest fragment around that bond, allowing you to rotate the fragment around the connection. If you have just added a fragment, it is selected automatically; otherwise, select the part you want to move.
Minimize while you build—or after
Interactive minimization can run during construction. Press Z or choose Edit > Minimize to switch it on; press Z again to stop. Seeing the structure respond as you build can help you assess how the growing molecule settles. You can also wait until the fragments are connected and minimize afterward.
Minimization does not replace checking which atoms and bonds you intended to connect. For example, the documentation notes that the Universal Force Field used by the interactive minimizer can affect the displayed bond order; depending on the file format used when saving, a bond may be saved as a single bond. When bond order matters, inspect it with the Edit bonds editor or select the bond and review it in the Inspector. Changing bond order through the Inspector does not automatically adjust hydrogens.
A useful habit is to build in short stages: place a fragment, inspect its attachment and orientation, then continue. If something goes wrong, undo is available through Edit > Undo. This keeps a complex build easier to troubleshoot than making many changes before checking the structure.
For more details on building with atoms and fragments, orienting structures, and editing hierarchy, see the SAMSON Building molecules guide.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at www.samson-connect.net.