Halogen bonding in ligand-receptor systems in the framework of classical force fields

Area of Science:

• Biochemistry
• Computational Chemistry
• Drug Discovery

Background:

• Halogen bonding is a crucial non-covalent interaction in protein-ligand complexes.
• Many pharmaceuticals contain halogens and form halogen bonds with biological targets.
• Traditional force fields struggle to model the electrostatic anisotropy of halogen bonds.

Purpose of the Study:

• To develop a computational method for accurately simulating halogen bonds in biomolecular systems.
• To improve molecular dynamics simulations of halogenated ligands interacting with proteins.

Main Methods:

• Introduction of pseudo-atoms on halogen atoms to model electrostatic potential anisotropy.
• Performing molecular dynamics simulations on protein-halogenated ligand complexes.
• Comparison of simulation results with experimental crystallographic data and QM/MM calculations.

Main Results:

• The pseudo-atom approach accurately describes the electrostatic potential anisotropy of halogens.
• Molecular dynamics simulations using this method reproduce experimental values for protein-ligand complexes.
• The findings align with crystallographic data and QM/MM results.

Conclusions:

• The pseudo-atom method provides a reliable way to study halogen bonding in drug discovery.
• This approach enhances the accuracy of molecular dynamics simulations for halogenated compounds.
• The method is validated against experimental and advanced computational data.