Relevance of Hydrogen Bonds for the Histamine H2 Receptor-Ligand Interactions: A Lesson from Deuteration.

ABSTRACT: We used a combination of density functional theory (DFT) calculations and the implicit quantization of the acidic N-H and O-H bonds to assess the effect of deuteration on the binding of agonists (2-methylhistamine and 4-methylhistamine) and antagonists (cimetidine and famotidine) to the histamine H2 receptor. The results show that deuteration significantly increases the affinity for 4-methylhistamine and reduces it for 2-methylhistamine, while leaving it unchanged for both antagonists, which is found in excellent agreement with experiments. The revealed trends are interpreted in the light of the altered strength of the hydrogen bonding upon deuteration, known as the Ubbelohde effect, which affects ligand interactions with both active sites residues and solvent molecules preceding the bindi

SUBMITTER: Krzan M 

PROVIDER: S-EPMC7072573 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature