Revisiting the halogen bonding between phosphodiesterase type 5 and its inhibitors.

ABSTRACT: Halogenated ligands are nowadays commonly designed in order to increase their potency against protein targets. Although novel computational methods of evaluating the affinity of such halogenated inhibitors have emerged, they still lack the sufficient accuracy, which is especially noticeable in the case of empirical scoring functions, being the method of choice in the drug design process. Here, we evaluated a series of halogenated inhibitors of phosphodiesterase type 5 with ab initio methods, revealing the physical nature of ligand binding and determining the components of interaction energy that are essential for proper inhibitor ranking. In particular, a nonempirical scoring model combining long-range contributions to the interaction energy provided a significant correlation with experime

SUBMITTER: Jedwabny W 

PROVIDER: S-EPMC6321839 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature