Computational Analysis of Histamine Protonation Effects on H₁R Binding.

ABSTRACT: Despite numerous studies investigating histamine and its receptors, the impact of histamine protonation states on binding to the histamine H1-receptor (H1R) has remained elusive. Therefore, we assessed the influence of different histamine tautomers (τ-tautomer, π-tautomer) and charge states (mono- vs. dicationic) on the interaction with the ternary histamine-H1R-G_q complex. In atomistic molecular dynamics simulations, the τ-tautomer formed stable interactions with the receptor, while the π-tautomer induced a rotation of the histamine ring by 180° and formed only weaker hydrogen bonding interactions. This suggests that the τ-tautomer is more relevant for stabilization of the active ternary histamine-H1R-G_q complex. In addition to the two monocationic tautomers, the bin

SUBMITTER: Conrad M 

PROVIDER: S-EPMC10180022 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature