Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis.

Acta Pharmacologica Sinica
Yuan-Qiang WangZhi-Wei Feng

Abstract

Serotonin (5-HT) receptors are proteins involved in various neurological and biological processes, such as aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation. They are commonly associated with drug abuse and addiction due to their importance as targets for various pharmaceutical and recreational drugs. However, due to a high sequence similarity/identity among 5-HT receptors and the unavailability of the 3D structure of the different 5-HT receptor, no report was available so far regarding the systematical comparison of the key and selective residues involved in the binding pocket, making it difficult to design subtype-selective serotonergic drugs. In this work, we first built and validated three-dimensional models for all 5-HT receptors based on the existing crystal structures of 5-HT1B, 5-HT2B, and 5-HT2C. Then, we performed molecular docking studies between 5-HT receptors agonists/inhibitors and our 3D models. The results from docking were consistent with the known binding affinities of each model. Sequentially, we compared the binding pose and selective residues among 5-HT receptors. Our results showed that the affinity variation could be potentially attributed to the selective resid...Continue Reading

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Citations

Sep 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lujing WangJianhui Liu
Nov 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nilupaier TayierYuan-Qiang Wang

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Software Mentioned

SYBYL
Captagon
Cytoscape
GAFF
Modeller
HTDocking
TargetHunter
Surflex
PubChem
- Dock GeomX ( SFXC

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