Sample input files

Protein structure file: 3OXC_edited.pdb. This is an edited version of the original structure of Wild Type HIV-1 Protease with Antiviral Drug Saquinavir (PDBID 3OXC). In this file the ligand molecule has been removed, and for residues with multiple occupancies only the A conformation is retained.

Ligand structure file: 3oxc_C_ROC.mol2. This is the structure of Saquinavir downloaded from PDB in mol2 format.

User Guide

PLIVA (Protein-Ligand Interaction Visualization and Analysis) helps you analyze and visualize interactions between proteins and ligands. Upload your structure files to generate interactive 2D diagrams, PyMOL scripts, and detailed interaction tables.

Quick Workflow:

  • Upload a protein structure file (PDB/ENT)
  • Upload a ligand structure file (SDF/MOL/MOL2)
  • PLIVA automatically detects various non-covalent interactions
  • View results in the 2D diagram or interactive table
  • Export as PNG/SVG, CSV, or PyMOL script

Uploading Files

PLIVA requires two structure files: a protein and its bound ligand. Upload them in the supported formats below.

Protein Structure

Required for analysis

  • Formats: PDB, ENT
  • Requirements: Include binding site residues
  • Note: The file must not contain the ligand molecule.

Ligand Structure

Required for analysis

  • Formats: SDF, MOL, MOL2
  • Requirements: Match the bound conformation
  • Note: Ensure atom names are standard for proper detection

Understanding the Results

2D Interaction Diagram

The interactive 2D diagram shows:

  • Central ligand: Your small molecule target, displayed with atom labels except carbons
  • Residue boxes: Protein residues arranged around the ligand
  • Colored lines: Different interactions between ligand and protein residues
  • Color coding: Each interaction type has a distinct color (see Diagram Customization)

Tip: You can drag ligand structure and residue labels to reposition them. The ligand structure can be rotated using right drag. The legend box can also be dragged to a different location on the canvas.

Interaction Details Table

The table displays all detected interactions with columns:

  • Type: Interaction classification (Hydrogen Bond, Van der Waals, etc.)
  • Protein Atom: Residue name, number, and atom identifier (e.g., "HIS 70 (CE1; NE2; CD2)")
  • Ligand Atom: Atom symbol and index in ligand structure
  • Distance (Å): Interatomic or ring centroid distance

Note: For pi-stacking and cation-pi interactions, protein and ligand atoms show all ring atoms involved (semicolon-separated).

Summary Panel

Right sidebar shows:

  • Total interactions: Count of unique residue-ligand interactions displayed
  • Breakdown by type: Number of each interaction type
  • Residues involved: Count of unique binding site residues
  • Ligand atoms: Count of ligand atoms making interactions

Diagram Customization

Personalize the appearance of your 2D interaction diagrams with various styling options.

Interaction cutoff can be adjusted using the slider. This controls which interactions are displayed in the 2D diagram. Note that this does NOT change the underlying interaction detection, which is based on specific criteria for each interaction type (see below).

Color Customization

Change the colors for each interaction type:

  • Hydrogen Bonds (default green)
  • Van der Waals (default grey)
  • Salt Bridges (default purple)
  • Pi-Stacking (default pink)
  • Cation-Pi (default amber)
  • Halogen Bonds (default cyan)
  • Hydrophobic (default brown)

Line Styles

Choose line styles for interaction connectors:

  • Solid: Continuous lines
  • Dash: Dashed lines
  • Dotted: Dotted lines

Other Options

  • Line Width: Adjust thickness of interaction lines
  • Label Font Size: Change size of residue labels
  • Show Hydrogen Labels: Display hydrogen atom labels in ligand
  • Show Legend: Toggle interactive legend in diagram

Tip: All customization changes are applied in real-time. Your preferences are preserved during the session.

Interaction Detection Methods

PLIVA uses a multi-method approach to detect various types of protein-ligand interactions. Below are the implementation details for each interaction type.

Hydrogen Bonds

Detection Criteria:

  • Distance cutoff: ≤ 3.5 Å between donor and acceptor
  • Donors: N-H and O-H groups
  • Acceptors: N and O atoms
  • Angle geometry: Donor-H-Acceptor angle ≥ 120°

Van der Waals Contacts

Detection Criteria:

  • Uses element-specific van der Waals radii
  • Distance cutoff: sum of vdW radii + 0.5 Å padding
  • Default cutoff: 4.0 Å for C-C interactions
  • Excludes hydrogen atoms
  • Detects weak hydrophobic packing

Salt Bridges

Detection Criteria:

  • Detects oppositely charged functional groups
  • Positive groups: ARG (NH1/NH2/NE), LYS (NZ), HIS (ND1/NE2)
  • Negative groups: ASP (OD1/OD2), GLU (OE1/OE2)
  • Distance cutoff: ≤ 5.0 Å
  • Requires formal charge difference

Pi-Stacking

Detection Criteria:

  • Identifies aromatic rings using ring detection algorithm
  • Protein aromatic residues: PHE, TYR, TRP, HIS
  • Ligand aromatic rings: 5- or 6-membered rings
  • Distance cutoff (centroid-to-centroid): ≤ 5.5 Å
  • Parallel stacking: 0-30° angle between ring normals (face-to-face)
  • T-shaped (edge-to-face): 60-90° angle between ring normals (perpendicular)
  • 30-60° range: rejected (unstable geometry)

Output includes: Ring atom lists (both protein and ligand) and geometry classification

Cation-Pi Interactions

Detection Criteria:

  • Positively charged residues: ARG (NH1/NH2/NE), LYS (NZ), HIS (ND1/NE2)
  • Ligand cations: N atoms with +1 formal charge
  • Aromatic rings: PHE, TYR, TRP, HIS (protein); any aromatic rings (ligand)
  • Distance cutoff (cation-centroid): ≤ 6.0 Å
  • Angle geometry: 45-90° between cation-centroid vector and ring normal

Halogen Bonds

Detection Criteria:

  • Halogens: F, Cl, Br, I atoms
  • Acceptors: N, O atoms with lone pairs
  • Distance cutoff: ≤ 3.5 Å
  • Geometry: C-X···A angle ≥ 145° (linear arrangement)
  • Halogen bonding is directional (C-X axis)

Hydrophobic Contacts

Detection Criteria:

  • Protein residues: ALA, VAL, LEU, ILE, MET, PHE, TRP, PRO, TYR
  • Ligand atoms: carbon and sulfur (non-charged)
  • Distance cutoff: ≤ 4.5 Å (adjustable via interaction cutoff)
  • Detects nonpolar-nonpolar interactions
  • Critical for ligand binding affinity

Interaction Prioritization: When multiple interactions occur between the same atom/residue pair, PLIVA retains only the highest priority interaction for 2D visualization.
The interaction order is as follows: Hydrogen Bonds (1) → Salt Bridges (2) → Pi-Stacking (3) → Cation-Pi (4) → Halogen Bonds (5) → Hydrophobic (6) → Van der Waals (7).
Note: All detected interactions are still listed in the interaction details table and included in exported csv file and PyMOL script.

Export Options

Export your analysis results in various formats.

PNG/SVG Images

  • High-quality images of the 2D interaction diagram
  • Includes all customizations (colors, line styles)
  • PNG: Raster format suitable for presentations
  • SVG: Vector format for publications (fully scalable)

CSV Data

  • Detailed interaction data table with columns:
  • Type: Interaction classification
  • Protein_Residue: Residue name and number
  • Protein_Atom: Atom name(s) (all ring atoms for pi-stacking)
  • Ligand_Atom: Atom symbol
  • Ligand_Index: Atom indices involved
  • Distance_A: Distance in Ångströms

PyMOL Script (.pml)

  • 3D visualization script for PyMOL molecular viewer
  • Requires PyMOL installed: pymol script.pml
  • Shows protein structure and ligand with interaction measurements
  • Distance labels for all detected interactions

Using PyMOL Scripts

The generated .pml file creates a 3D view in PyMOL with:

  • Protein shown as cartoon with interacting residues highlighted
  • Ligand displayed as sticks with atom labels
  • Distance measurements for all detected interactions
  • Color coding matching your PLIVA diagram
  • Labeled residues for easy identification
If you need further assistance, please contact us via our form.