The Effect of Deuteration on the H2 Receptor Histamine Binding Profile: A Computational Insight into Modified Hydrogen Bonding Interactions.

ABSTRACT: We used a range of computational techniques to reveal an increased histamine affinity for its H2 receptor upon deuteration, which was interpreted through altered hydrogen bonding interactions within the receptor and the aqueous environment preceding the binding. Molecular docking identified the area between third and fifth transmembrane α-helices as the likely binding pocket for several histamine poses, with the most favorable binding energy of -7.4 kcal mol-1 closely matching the experimental value of -5.9 kcal mol-1. The subsequent molecular dynamics simulation and MM-GBSA analysis recognized Asp98 as the most dominant residue, accounting for 40% of the total binding energy, established through a persistent hydrogen bonding with the histamine -NH3+ group, the latter further held in place

SUBMITTER: Hok L 

PROVIDER: S-EPMC7766521 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature