NCI-Profiler

NCI-Profiler automatically detects and visualizes nine types of protein–ligand non-covalent interactions from PDB or mmCIF coordinates using literature-derived geometric criteria.

Key Features:

• Interaction Detection: Detects hydrogen bonds, hydrophobic contacts, salt bridges, π–π stacking, cation–π, halogen bonds, metal coordination with τ4/τ5 geometry analysis, water bridges, and halogen–water–hydrogen (XWH) bridges.
• Input Handling: Accepts PDB/mmCIF files or PDB IDs without manual structure preparation, and handles multi-ligand and macrocyclic ligands.
• Output Generation: Produces editable 2D diagrams, an in-browser Mol* 3D view, PyMOL sessions, and JSON/CSV/TXT output files.
• Deployment Options: Available as a free web server and a dependency-free Python CLI/API.
• Performance Validation: Achieved F1-scores of 92–100% for π–π stacking, metal coordination, and water bridges, and 77–83% for the remaining types except hydrophobic contacts (54.8%); detected literature-confirmed interactions more completely than PLIP in five of nine categories and ran roughly twice as fast.

Scientific Applications:

• Binding Pocket Analysis: Reveals binding-pocket growth vectors through expanded interaction coverage.
• Structure–Activity Relationship Explanation: Explains structure–activity trends in protein–ligand complexes.
• Receptor Selectivity Determination: Distinguishes receptor-subtype selectivity based on interaction profiles.
• Comprehensive Interaction Profiling: Replaces fragmented analysis across multiple programs with unified detection of metal coordination, XWH bridges, and macrocyclic ligand interactions.

Methodology:

NCI-Profiler detects interactions directly from PDB or mmCIF coordinates using literature-derived geometric criteria, without manual structure preparation. Accuracy was validated against 85 literature-annotated complexes and directly compared against PLIP on the same dataset.