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Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor-Ligand Interactions.

ABSTRACT: Here, we predicted the potential halogen bonding interaction between compound 2 and the 5-hydroxytryptamine 2B (5-HT_2B) receptor and systematically assessed this interaction via structure-activity relationship analysis and molecular dynamics simulations. A physics-based computational protocol was then developed to further explore the opportunity of "designing in" halogen bonding interactions in structure-based ligand design for the 5-HT_2B receptor, which not only facilitated the identification of previously uncharacterized halogen bonds in known 5-HT_2B ligands but also enabled the rational design of halogen bonding interactions for the optimization of 5-HT_2B ligands. As a proof-of-concept, a series of halogen-substituted analogues of doxepin was synthesized and evaluated, which showed improved in vitro and in vivo potency.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6187415 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor-Ligand Interactions.

Zhou Yu Y Wang Yuanxun Y Li Pengfei P Huang Xi-Ping XP Qi Xiangbin X Du Yunfei Y Huang Niu N

ACS medicinal chemistry letters 20181001 10

Here, we predicted the potential halogen bonding interaction between compound 2 and the 5-hydroxytryptamine 2B (5-HT2B) receptor and systematically assessed this interaction via structure-activity relationship analysis and molecular dynamics simulations. A physics-based computational protocol was then developed to further explore the opportunity of "designing in" halogen bonding interactions in structure-based ligand design for the 5-HT2B receptor, which not only fac ...[more]

PMID: 30344910

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