Connexin hemichannels mediate cytoplasm and extracellular milieu communication by exchanging a variety of cytoplasmic molecules and ions. These hemichannels can be regulated by external stimuli such as mechanical stress, applied voltage, pH and temperature changes. Although there are many studies on structures and functions of connexin 26 in contexts of pH, ion concentration and voltage, employing computational methods, no such study has been performed so far involving temperature changes. In this study, using molecular dynamics simulation, we investigate thermosensitivity of the human Connexin 26 hemichannel. Our results show that the channel approaches a structurally closed state at lower temperature compared to higher temperature. This is in fair agreement with experimental results that indicate channel closure at lower temperature. Furthermoer, our MD simulation results show that some regions of connexin 26 hemichannel are more sensitive to temperature compared to other regions. Whereas the intercellular half of the channel does not show any considerable response to temperature during the simulation time accessible in this study, the cytoplasmic half approaches a closed structural state at lower temperature compared to the higher temperature. Specifically, our results suggest that the cytoplasmic loop, the cytoplasmic half of the second transmembrane helix, and the N-terminus helix play a dominant role in temperature gating.

连接蛋白半通道通过交换多种细胞质分子和离子来介导细胞质和细胞外环境通讯。这些半通道可通过外部刺激（例如机械应力，施加的电压，pH和温度变化）进行调节。尽管在pH，离子浓度和电压的背景下对连接蛋白26的结构和功能进行了许多研究，但仍采用计算方法，但迄今为止尚未进行涉及温度变化的此类研究。在这项研究中，使用分子动力学模拟，我们研究了人类连接蛋白26半通道的热敏感性。我们的结果表明，与较高的温度相比，该通道在较低的温度下接近结构封闭状态。这与表明较低温度下通道关闭的实验结果完全吻合。更进一步，我们的MD模拟结果表明，与其他区域相比，连接蛋白26半通道的某些区域对温度更敏感。尽管在本研究可访问的模拟时间内，通道的细胞间一半对温度没有任何显着响应，但与较高温度相比，细胞质的一半在较低温度下接近封闭的结构状态。具体而言，我们的结果表明，胞质环，第二个跨膜螺旋的胞质一半和N末端螺旋在温度门控中起主导作用。尽管在本研究可访问的模拟时间内，通道的细胞间一半对温度没有任何显着响应，但与较高温度相比，细胞质的一半在较低温度下接近封闭的结构状态。具体而言，我们的结果表明，胞质环，第二个跨膜螺旋的胞质一半和N末端螺旋在温度门控中起主导作用。尽管在本研究可访问的模拟时间内，通道的细胞间一半对温度没有任何显着响应，但与较高温度相比，细胞质的一半在较低温度下接近封闭的结构状态。具体而言，我们的结果表明，胞质环，第二个跨膜螺旋的胞质一半和N末端螺旋在温度门控中起主导作用。