From a crowded structure to a useful binding-site shortlist

A molecular structure can contain far more than the atoms you need to inspect: solvent, ions, glycans, alternate conformations, and residues far from the binding site. The challenge is not simply finding atoms near a ligand. It is making a selection that answers a specific question, then refining it without losing track of what the selection means.

SAMSON’s Node Specification Language (NSL) lets you express these questions as selections. A practical starting point is to identify receptor residues close to a ligand, then choose whether you need whole residues, individual atoms, or a particular chemical subset. The examples below show how to build that shortlist and investigate it from several angles.

Start with nearby residues

To find receptor residues within 5 Å of a ligand, use:

(n.t r w 5A of n.c lig) and (n.t r in n.c rec)

The first part specifies the distance relationship; the second restricts the result to receptor residues. Keeping these conditions visible is useful: it makes clear both where the selection is and what kind of structure it includes. For a residue-level view, this is often more useful than starting with every atom in the structure.

If you want the atoms belonging to nearby residues, select atoms in the residue selection:

n.t a in (n.t r w 5A of n.c lig)

This distinction matters when preparing a view or analysis. A residue-level selection helps identify which amino acids line the pocket; an atom-level selection is more targeted for inspecting contacts or geometry.

Separate direct contacts from the surrounding pocket

A 5 Å neighborhood is a useful way to define a pocket region, but it is not the same as a tight contact. For example, the documentation gives this expression for ligand atoms within 2 Å of receptor atoms:

(n.t a in n.c lig) w 2A of n.c rec

For a stricter steric-clash shortlist, the example uses a 2.2 Å cutoff and excludes hydrogen atoms on both sides:

((n.t a in n.c lig) and not a.s H) w 2.2A of ((n.t a in n.c rec) and not a.s H)

These selections answer different questions. A broader neighborhood helps map the pocket; a very short heavy-atom separation flags close approaches worth checking. Treat the distance as a filter for inspection, not as a verdict about whether a structure is wrong.

Check whether waters are part of the picture

Water can be relevant to a binding-site interpretation, so it can help to examine it separately from the protein. This expression selects water within 4 Å of any ligand:

n.c wat w 4A of n.c lig

To find water oxygens positioned within 3 Å of both receptor and ligand, use:

(a.s O in n.c wat) and (n.t a w 3A of n.c rec) and (n.t a w 3A of n.c lig)

The latter is a focused way to look for possible bridging waters. It does not, by itself, establish that a water forms a functional bridge; it identifies candidates by atom type and distance so you can inspect them in context.

Refine the shortlist by chemistry

Once you have a spatial region, NSL can narrow it by residue or atom properties. For example, aromatic residues within 5 Å of the ligand can be selected with:

(r.t PHE,TYR,TRP,HIS) and (n.t r w 5A of n.c lig)

To focus on polar oxygen and nitrogen atoms in the receptor within 3 Å, use:

(a.s O,N in n.c rec) w 3A of n.c lig

These filters make the selection more interpretable: instead of looking at every nearby atom, you can ask which aromatic residues or polar atoms are close enough to merit attention. The same general pattern works throughout the examples: define a structural category, apply a distance condition, and add exclusions or additional properties only when they serve the question.

A small workflow for clearer selections

  1. Choose the target level. Decide whether the question concerns residues, atoms, or a specific atom subset.
  2. Set a distance that matches the question. A pocket neighborhood and a tight-contact screen are not interchangeable.
  3. Limit the structural category. Use receptor, ligand, or water conditions to avoid mixing unrelated components.
  4. Add chemical filters. Narrow the result to atom types or residue types relevant to the interaction you are investigating.
  5. Inspect the result in context. A selection identifies candidates; interpretation still depends on the surrounding structure and the purpose of the analysis.

Thinking in these steps turns a long selection expression into a sequence of understandable decisions. It also makes it easier to adapt the selection when the question changes—for example, from mapping a pocket to checking polar contacts or locating nearby waters.

For more NSL selection examples, see the SAMSON NSL examples reference.

Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.

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