Building a molecule atom by atom can be slow. Building from fragments is faster, but it introduces a familiar problem: a fragment can attach at the wrong place, overlap the structure, or leave you unsure whether the connection is sensible. A reliable workflow is to choose the connection deliberately, let the builder help with placement, and check the result as you go.
In SAMSON, the Add editor supports both individual atoms and larger assets, such as rings, functional groups, and molecules. The Asset Browser provides built-in assets and assets available through SAMSON Connect. You can search using Filter assets…, then switch between grid and list views to find a suitable starting point.
Choose how the fragment should connect
Before placing a fragment, decide which atom or bond should form the connection. There are two common approaches:
- Substitution: hover over the atom you want to replace, then click. The selected atom in the incoming fragment replaces it.
- Bond connection: press and hold on the atom you want to connect to, move the cursor away, and release at a bond-like distance.
These methods solve different modeling needs. Substitution is useful when replacing a hydrogen or another existing atom with a group. A bond connection is useful when attaching a fragment without replacing the target atom. SAMSON positions added atoms and fragments with covalent radii in mind, but the connection point still matters.
If the asset’s default attachment point is not the one you need, you can change it. Hold Ctrl on Windows/Linux or Cmd on macOS, then choose the desired atom in the fragment. For substitutions, holding Shift lets you choose which atom and bond in the asset are used for the replacement. These controls can prevent a common source of frustration: a fragment that looks right but attaches through the wrong part of its structure.
Let the builder flag questionable connections
Before building, check Preferences > Editors > Add. Several options can make the workflow easier to inspect:
- Automatically orient fragments on substitution positions a fragment to reduce overlap with the existing molecule.
- Prevent unexpected substitutions shows acceptable operations with a green overlay and forbidden ones with a red overlay.
- Adjust hydrogens when adding fragments… adjusts hydrogens, as best as possible, when adding or linking atoms and fragments, changing bond order, or changing formal charge.
- Merge neighboring atoms merges atoms that are close enough when a fragment is connected.
The overlays are a prompt to pause and check the proposed operation—not a substitute for understanding the chemistry you intend to model. If an operation is red, check the target atom and the fragment’s substitution atom before proceeding. You can change the relevant preferences if you need to override the recommendations.
A practical sequence: assemble, inspect, relax
For example, when combining phenol fragments, first choose the phenol asset in the Asset Browser. Add the first molecule by clicking in the Viewport, then attach further fragments using substitution or bond connections. If the default attachment point is unsuitable, choose another atom in the fragment with Ctrl/Cmd before making the connection.
For a more involved example, the documentation builds Bisphenol A from a propane backbone and two phenol fragments. The key is to prepare the backbone, select the phenol asset, change its substitution atom to the intended carbon, and replace two hydrogens on the middle carbon with phenol fragments. Watch the orientation preview and the green or red overlay as you place each group. This incremental approach makes it easier to notice an incorrect attachment while it is still easy to undo.
Interactive minimization can be switched on with Z or through Edit > Minimize. It can run while you build, helping you see the structure relax as connections are made. Press Z again to stop it. Minimization helps with geometry; it does not replace checking that you chose the intended atoms and bonds.
After placement, use the Local Move Editor (M) to adjust a fragment’s orientation. Clicking a bond lets the editor select the shortest fragment around it, which is useful when you want to rotate part of a molecule around that bond. If you edit bond order through the Inspector, note that hydrogens will not be adjusted automatically in that workflow. The Edit bonds editor is another option for changing bond order interactively.
And if a step goes wrong, use Edit > Undo rather than trying to compensate with additional edits. Small, deliberate operations—choose the connection, inspect the preview, place the fragment, then adjust or minimize—make larger structures much easier to build and review.
For the full workflow and additional examples, see the SAMSON guide to building molecules.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at www.samson-connect.net.