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Updated: Sep 30, 2025
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From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding
Published on: March 24, 2018
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Halogen Bonds Exist between Noncovalent Ligands and Natural Nucleic Acids
Kaijie Mu1,2, Zhengdan Zhu1,3, Amina Abula1
1CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Journal of Medicinal Chemistry
|March 11, 2022
Summary
Nucleic acids (NAs) can accept halogen bonds (XBs) from noncovalent ligands, contrary to previous assumptions. This study confirms XBs in 13 systems, offering insights for drug design targeting NAs.
Area of Science:
- Biochemistry
- Chemical Biology
- Drug Discovery
Background:
- Nucleic acids (NAs) possess electron-rich properties suggesting potential as halogen bond (XB) acceptors.
- Previous database surveys indicated no XBs formed between noncovalent ligands and NAs.
Purpose of the Study:
- To investigate the underestimation of XB formation between NAs and noncovalent ligands.
- To explore the potential of NAs as XB acceptors in molecular interactions.
- To provide insights for rational drug design targeting NAs.
Main Methods:
- Statistical analysis of the Protein Data Bank (PDB) database.
- Quantum-mechanics/molecular-mechanics (QM/MM) optimizations.
- Energy calculations, natural bond orbital (NBO) analysis, and noncovalent interaction (NCI) analysis.
Main Results:
- XBs between natural NAs and noncovalent ligands are often underestimated.
- NAs can effectively serve as XB acceptors for noncovalent halogen ligands.
- XBs were confirmed in 13 systems, with two (445D and 4Q9Q) exhibiting strong interactions.
- Geometric rules for XB formation in NAs were elucidated through energy scanning of model systems.
Conclusions:
- This research validates the role of NAs as XB acceptors.
- The findings provide a foundation for utilizing XBs in the rational design of NA-targeting drugs.
- Understanding XB interactions with NAs opens new avenues in medicinal chemistry.
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