The article by Pascal Auflinger, Franklin A. Hays, Eric Westhof, and P. Shing Ho explores the role of halogen bonds in biological molecules, particularly proteins and nucleic acids. Halogen bonds, defined as short C-X=O-Y interactions where X is a halogen (chlorine, bromine, or iodine) and Y is a functional group like carbonyl, hydroxyl, or phosphate, have been recognized in organic chemistry since the 1950s. These bonds are characterized by distances shorter than the sum of their van der Waals radii and angles that are typically around 165° for C-X-O and 120° for X-O-Y. The study reveals that halogen bonds can significantly affect ligand binding and molecular folding, with applications in drug design and nanotechnology. The authors surveyed protein and nucleic acid structures in the Protein Data Bank (PDB) to identify halogen bonds. They found that halogen bonds are prevalent in biological systems, particularly in thyroid hormones and halogenated metabolites. The geometry of halogen bonds in biological systems deviates from the ideal small molecule geometry due to the complex environments found in biomolecules, such as the involvement of π-electrons in peptide bonds. The study also highlights the importance of halogen bonds in altering conformational equilibria, as seen in the crystallization of specific DNA sequences with bromine or iodine substitutions. The article concludes that halogen bonds offer new tools for molecular design, particularly in the context of drug development and nanotechnology. However, it also cautions that the introduction of halogen atoms into biomolecular systems can lead to unexpected conformational effects, emphasizing the need for careful consideration in molecular dynamics simulations and force-field models.The article by Pascal Auflinger, Franklin A. Hays, Eric Westhof, and P. Shing Ho explores the role of halogen bonds in biological molecules, particularly proteins and nucleic acids. Halogen bonds, defined as short C-X=O-Y interactions where X is a halogen (chlorine, bromine, or iodine) and Y is a functional group like carbonyl, hydroxyl, or phosphate, have been recognized in organic chemistry since the 1950s. These bonds are characterized by distances shorter than the sum of their van der Waals radii and angles that are typically around 165° for C-X-O and 120° for X-O-Y. The study reveals that halogen bonds can significantly affect ligand binding and molecular folding, with applications in drug design and nanotechnology. The authors surveyed protein and nucleic acid structures in the Protein Data Bank (PDB) to identify halogen bonds. They found that halogen bonds are prevalent in biological systems, particularly in thyroid hormones and halogenated metabolites. The geometry of halogen bonds in biological systems deviates from the ideal small molecule geometry due to the complex environments found in biomolecules, such as the involvement of π-electrons in peptide bonds. The study also highlights the importance of halogen bonds in altering conformational equilibria, as seen in the crystallization of specific DNA sequences with bromine or iodine substitutions. The article concludes that halogen bonds offer new tools for molecular design, particularly in the context of drug development and nanotechnology. However, it also cautions that the introduction of halogen atoms into biomolecular systems can lead to unexpected conformational effects, emphasizing the need for careful consideration in molecular dynamics simulations and force-field models.