Targeting Protein Pockets with Halogen Bonds: The Role of the Halogen Environment

BOGADO, MARÍA LUCRECIA; VILLAFAÑE, ROXANA NOELIA; GÓMEZ CHAVEZ, JOSÉ LEONARDO; ANGELINA, EMILIO LUIS; SOSA, GLADIS LAURA; PERUCHENA, NÉLIDA MARÍA

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Año: 2022 vol. 62 p. 6494 - 6507

1549-9596

Protein pockets that form a halogen bond (X-bond) with a halogenated ligand molecule simultaneously form other (mainly hydrophobic) interactions with the halogen atom that can be considered as its "X-bond environment"(XBenv). Most studies in the field have focused on the X-bond, with the properties of the XBenv usually overlooked. In this work, we derived a protocol that evaluates the XBenv strength as a measure of the propensity of a protein pocket to host an X-bond. The charge density-based topological descriptors in combination with machine learning tools were employed to predict formation and strength of the interactions that conform the XBenv as a function of their geometrical parameters. On the basis of these results, we propose that the XBenv can be used as a footprint to judge the chance of a protein pocket to form an X-bond.