Transient receptor potential vanilloid subtype 1 (TRPV1) is a polymodel sensory receptor and can be activated by moderate temperature (≥ 43 °C). Though extensive researches on the heat-activation mechanism revealed some key elements that participate in the heat-sensation pathway, the detailed thermal-gating mechanism of TRPV1 is still unclear. We investigate the heat-activation process of TRPV1 channel using the molecular dynamics simulation method at different temperatures. It is found that the favored state of the supposed upper gate of TRPV1 cannot form constriction to ion permeation. Oscillation of S5 helix originated from thermal fluctuation and forming/breaking of two key hydrogen bonds can transmit to S6 helix through the hydrophobic contact between S5 and S6 helix. We propose that this is the pathway from heat sensor of TRPV1 to the opening of the lower gate. The heat-activation mechanism of TRPV1 presented in this work can help further functional study of TRPV1 channel....

中文翻译：

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确定TRPV1通道打开概率的不同温度下S5螺旋的振荡

瞬态受体电位类香草酸亚型1（TRPV1）是一种多模型感觉受体，可以在中等温度（≥43°C）下激活。尽管对热活化机制的广泛研究揭示了参与热敏途径的一些关键因素，但TRPV1的详细热门控机制仍不清楚。我们使用分子动力学模拟方法在不同温度下研究TRPV1通道的热活化过程。已经发现，假定的TRPV1上栅极的良好状态无法形成对离子渗透的限制。S5螺旋的振荡起因于热波动，两个关键氢键的形成/断裂可通过S5和S6螺旋之间的疏水接触传递到S6螺旋。我们建议这是从TRPV1的热传感器到下闸门打开的路径。这项工作中提出的TRPV1的热激活机制可以帮助进一步研究TRPV1通道的功能。