Profile protein-ligand interactions from a PDB complex structure. Learn more
What is PLIP?
PLIP, the Protein-Ligand Interaction Profiler, detects noncovalent contacts in three-dimensional protein-ligand complexes. It applies geometric rules to identify hydrophobic contacts, hydrogen bonds, water bridges, salt bridges, pi stacking, pi-cation interactions, halogen bonds, and metal complexes.
PLIP describes interactions present in a submitted pose. It does not dock the ligand, calculate binding affinity, or prove that a contact is energetically favorable. Its main value is turning a complex structure into a reproducible interaction inventory that can be compared across crystal structures, docking poses, and designed complexes.
How to use PLIP online
Run PLIP online by uploading a protein-ligand complex in PDB format or fetching one from RCSB. The structure must contain protein ATOM records and at least one non-water ligand encoded as HETATM. ProteinIQ returns one row per detected interaction together with PLIP's XML report, text report, processed structure, and logs.
Input requirements
| Input | Requirements |
|---|---|
Protein-ligand complex | One .pdb or .ent file, or one RCSB PDB ID. Protein and ligand must already share the same coordinate frame. |
| Protein records | At least one protein atom represented by an ATOM record. |
| Ligand records | At least one non-water ligand represented by HETATM records. |
A separate receptor file and ligand file cannot be submitted to this tool. They must first be combined into one valid complex PDB. Small molecules written as ATOM records may be interpreted as part of the protein and should be re-exported as HETATM.
Settings
| Setting | Description |
|---|---|
PDB model | Selects the model from a multi-model PDB. The default is model 1. |
Skip hydrogen addition | Runs PLIP without adding polar hydrogens. Leave off for the standard behavior. Enable only when the supplied hydrogen model should remain authoritative. |
Hydrogen placement influences donor and acceptor geometry. Protonation states, missing atoms, alternate locations, and unresolved waters can therefore change the interaction profile even when the heavy-atom pose is unchanged.
Results
The interaction table begins with the complex and binding-site identity, then includes fields specific to each contact type.
| Field | Meaning |
|---|---|
interaction_type | PLIP contact class, such as hydrogen_bond, hydrophobic_interaction, or pi_stack. |
binding_site_uid | Combined identifier for the PDB entry and ligand site. |
ligand_hetid, ligand_chain, ligand_position | Ligand residue identity in the PDB complex. |
resnr, restype, reschain | Interacting protein residue number, residue type, and chain when reported for that interaction. |
distance_angstrom | Principal atom or group distance normalized to Å when the PLIP report supplies one. |
| Interaction-specific fields | Donor and acceptor indices, angles, ring geometry, charge centers, water atoms, or metal coordination details. |
The exact columns vary because hydrogen bonds, pi interactions, and metal complexes require different geometric descriptions. The Files tab preserves the complete XML and text reports for analyses that need every native PLIP field.
How PLIP detects interactions
PLIP assigns functional groups and then evaluates distance and angle rules for each interaction class. Hydrogen bonds use donor-acceptor geometry, pi stacking uses aromatic ring centers, plane angles, and offsets, and salt bridges use the distance between opposite charge centers. Water bridges require one water molecule positioned between compatible protein and ligand donor-acceptor groups.
Hydrophobic contacts receive additional reduction steps. When several nearby atoms describe essentially the same residue-level contact, PLIP keeps representative shortest contacts so that large hydrophobic groups do not overwhelm the interaction list.
Interpreting a PLIP profile
Contact counts are best used as descriptors, not as a binding score. A pose with more contacts is not automatically better: one well-oriented hydrogen bond or metal coordination may be more meaningful than several marginal hydrophobic contacts, and strained ligand geometry can still produce an attractive-looking profile.
Practical review should include:
- Residue identity: Check whether contacts involve known catalytic, recognition, or resistance residues.
- Geometry: Inspect distances and angles near method cutoffs rather than treating all detected contacts as equally strong.
- Conservation across poses: Contacts repeated across independently generated poses are more informative than a contact unique to one orientation.
- Structure preparation: Confirm protonation, cofactors, metals, waters, alternate conformations, and missing side chains.
ProLIF is better suited to compact interaction fingerprints across many poses. PLIP is better when a detailed, human-readable interaction report for a complex is needed. Before interpreting a generated pose, PoseBusters can check whether its ligand chemistry and receptor placement are physically plausible.
