Protein-Ligand Interaction Types Explained: H-Bonds, pi-pi Stacking, Salt Bridges and Friends

By BioDockify Computational Research Team · October 17, 2026 · Reference

The complete field guide to protein-ligand interactions: hydrogen bonds, ionic pairs, pi-system contacts, hydrophobics, halogen bonds and water-mediated contacts - strengths, geometry, distance criteria, and how to read them in docking diagrams.

Read the complete article with tables, code and references on BioDockify.

Key References

• Bissantz, C., Kuhn, B. & Stahl, M. A medicinal chemist's guide to molecular interactions. J. Med. Chem. 53, 5061-5084 (2010).
• Salentin, S., Schreiber, S., Haupt, V.J. et al. PLIP: fully automated protein-ligand interaction profiler. Nucleic Acids Res. 43, W443-W447 (2015). DOI: 10.1093/nar/gkv315
• Lipinski, C.A. et al. Experimental and computational approaches to estimate solubility and permeability. Adv. Drug Deliv. Rev. 23, 3-25 (1997). DOI: 10.1016/S0169-409X(96)00423-1
• Davis, A.M. & Teague, S.J. Hydrogen bonding, hydrophobic interactions, and failure of the rigid receptor hypothesis. Angew. Chem. Int. Ed. 38, 768-790 (1999).

Scope & Limitations

Interaction counts are not energies - strength depends on burial, desolvation costs and context; more contacts does not mean stronger binding Geometric criteria are conventions: a 3.5 A cutoff admits weak contacts and excludes strained strong ones; report the criteria your tool used