Halogen bonding in halocarbon-protein complexes and computational tools for rational drug design

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Drug Design

Background:

• Halogens play a significant role in modern drug design, enhancing ADME properties.
• Halogen bonds, a type of non-covalent interaction involving halogens as electrophilic species, are increasingly recognized in protein-ligand recognition.

Purpose of the Study:

• To review computational methodologies capable of accurately describing halogen bonds in protein-ligand complexes.
• To provide insights into the application of these methods in computer-aided drug design.

Main Methods:

• Review of existing computational tools for modeling halogen bonds.
• Discussion of various methods, from fast screening to Quantum Mechanics (QM) calculations.

Main Results:

• Current computational tools for halogen bonding are not yet standardized in scientific literature.
• Advancements in computational methods are enabling better descriptions of halogen-protein interactions.

Conclusions:

• Despite progress, computational methods for halogen bonding require further development and integration into standard drug design workflows.
• Improving the handling of desolvation effects in halogenated species is a key strategy for enhancing computational accuracy.