NCI-Profiler: automated protein-ligand interaction detection and visualization
- 1Kyung Hee University
Abstract
Non-covalent interactions govern ligand binding specificity and affinity, but existing analysis tools cover a limited set of interaction types, treat metal coordination as a generic contact, and struggle to depict macrocyclic ligands such as heme or cobalamin, leaving comprehensive interaction analysis fragmented across multiple programs. We developed Non-Covalent Interaction Profiler (NCI-Profiler), a free web-based and command-line tool for automated detection and visualization of nine types of protein-ligand non-covalent interactions, including metal coordination and halogen-water-hydrogen (XWH) bridges. NCI-Profiler detects interactions directly from PDB or mmCIF coordinates using literature-derived geometric criteria, without manual structure preparation, and produces interactive 2D diagrams, an in-browser three-dimensional viewer, and downloadable 3D PyMOL sessions, together with structured output files. Its accuracy was validated against 85 literature-annotated complexes and directly compared against PLIP, an established interaction-detection tool, on the same dataset. NCI-Profiler achieved F1-scores of 92-100% for {pi}-{pi} stacking, metal coordination, and water bridges, and 77-83% for the remaining types except hydrophobic contacts (54.8%); it detected literature-confirmed interactions more completely than PLIP in five of nine categories and ran roughly twice as fast. Three case studies further show its expanded coverage can reveal binding-pocket growth vectors, explain structure-activity trends, and distinguish receptor-subtype selectivity. NCI-Profiler is freely available at https://ncip.khu.ac.kr.
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BibTeX
@misc{sharma2026nciprofiler,
title = {{NCI-Profiler: automated protein-ligand interaction detection and visualization}},
author = {R. Sharma and E. Y. Lee},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.11.758375},
url = {https://www.biorxiv.org/content/10.64898/2026.10.11.758375v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - NCI-Profiler: automated protein-ligand interaction detection and visualization
AU - R. Sharma
AU - E. Y. Lee
PY - 2026
DA - 2026/10/11
PB - bioRxiv
DO - 10.64898/2026.10.11.758375
UR - https://www.biorxiv.org/content/10.64898/2026.10.11.758375v1
AB - Non-covalent interactions govern ligand binding specificity and affinity, but existing analysis tools cover a limited set of interaction types, treat metal coordination as a generic contact, and struggle to depict macrocyclic ligands such as heme or cobalamin, leaving comprehensive interaction analysis fragmented across multiple programs. We developed Non-Covalent Interaction Profiler (NCI-Profiler), a free web-based and command-line tool for automated detection and visualization of nine types of protein-ligand non-covalent interactions, including metal coordination and halogen-water-hydrogen (XWH) bridges. NCI-Profiler detects interactions directly from PDB or mmCIF coordinates using literature-derived geometric criteria, without manual structure preparation, and produces interactive 2D diagrams, an in-browser three-dimensional viewer, and downloadable 3D PyMOL sessions, together with structured output files. Its accuracy was validated against 85 literature-annotated complexes and directly compared against PLIP, an established interaction-detection tool, on the same dataset. NCI-Profiler achieved F1-scores of 92-100% for {pi}-{pi} stacking, metal coordination, and water bridges, and 77-83% for the remaining types except hydrophobic contacts (54.8%); it detected literature-confirmed interactions more completely than PLIP in five of nine categories and ran roughly twice as fast. Three case studies further show its expanded coverage can reveal binding-pocket growth vectors, explain structure-activity trends, and distinguish receptor-subtype selectivity. NCI-Profiler is freely available at https://ncip.khu.ac.kr.
ER -