Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Biophys Chem. 2022 Oct;289:106862. doi: 10.1016/j.bpc.2022.106862. Epub 2022 Jul 30.
MhOR5, an insect olfactory receptor (OR), has an occluded binding site for the odorant eugenol in both the open and closed states of the ion channel. We used atomistic molecular dynamics simulation (MD) and steered molecular dynamics to examine possible tunnels to the odorant binding site from the protein surface. Four high probability tunnels were identified in the MD results. Surprisingly, three of the tunnels connect the ligand binding site to the lipid bilayer. We found sharp 30%-50% increases or decreases in tunnel bottleneck areas over 70 nsec MD trajectories, both in the ligand-bound and unliganded OR structures. Steered MD showed that eugenol follows the tunnels to the protein surface, and the potential of mean force is quantitatively consistent with the known affinity of eugenol for MhOR5. We examined AlphaFold-generated models of 21 other insect ORs, and we found that 19 had odorant binding sites and tunnels in similar positions to MhOR5. The possibility of a tunnel between the odorant binding site and the lipid bilayer in insect ORs suggests new experiments to test molecular mechanisms for insect odorant reception.
MhOR5 是一种昆虫嗅觉受体 (OR)，在离子通道的开放和关闭状态下，其嗅味剂丁香酚都有一个被封闭的结合位点。我们使用原子分子动力学模拟 (MD) 和导向分子动力学来研究从蛋白质表面到气味结合位点的可能隧道。在 MD 结果中确定了四个高概率隧道。令人惊讶的是，其中三个隧道将配体结合位点与脂质双层连接起来。我们发现，在配体结合和未配体结合的 OR 结构中，70 纳秒 MD 轨迹中隧道瓶颈区域的尖锐增加或减少了 30%-50%。导向 MD 表明丁香酚沿着隧道到达蛋白质表面，平均力势的势能与丁香酚对 MhOR5 的已知亲和力定量一致。我们检查了 21 种其他昆虫 OR 的 AlphaFold 生成模型，发现其中 19 种具有类似 MhOR5 位置的气味结合位点和隧道。昆虫 OR 中气味结合位点和脂质双层之间隧道的可能性提出了新的实验来测试昆虫气味受体的分子机制。
