Work

The Interaction Mechanism Between C14-Polyacetylene Compounds and the Rat TRPA1 Receptor: An In Silico Study

Year: 2024

Type: article

Abstract: Polyacetylene (PA) compounds, as natural products, exhibit remarkable properties and distinctive chemical activities. Three structurally similar C14-PA compounds-Echinophorin D, Echinophorin B, and Echinophorin A-extracted from plants demonstrate varying biological activities on the Transient Receptor Potential Channel A1 (TRPA1) protein, which belongs to the TRP (Transient Receptor Potential) family. In the current study, we investigated the binding modes of these three PA compounds with TRPA1 using molecular dynamics (MD), molecular docking, binding free energy calculations, and quantum mechanics/molecular mechanics (QM/MM) methods. Initially, a putative binding site (site-II) in TRPA1 was identified for these compounds; Echinophorin B was found to stabilize the upward A-loop of TRPA1, which is critical for its activation. Furthermore, the binding affinity calculations of PA compounds through molecular fragment decomposition indicate that the arrangement of two triple bonds and one double bond in C14-PA compounds is vital for regulating TRPA1 bioactivity. Additionally, the lipophilic and electronic properties of the three molecules were analyzed in relation to binding affinity, establishing a correlation between TRPA1 activity and these molecular properties.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms252011290

Authors: Hui Yu, Denghui Gao, Ying Yang, Lu Liu, Xi Zhao, Risong Na

Institutions: Beihua University, Northeast Normal University, Henan Agricultural University, Jilin University

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,296

Funder: National Natural Science Foundation of China