Protein Choreography of the Molecular Compass. PhD in Biosciences. (BBSRC SWBio DTP) 4268

鸟类、果蝇和许多其他动物都具有非凡的能力，可以通过隐花色素蛋白的生化反应来感知地球的磁场。令人惊讶的是，这种蛋白质分子罗盘利用真正的量子效应来响应动物导航时磁场的变化。这些蛋白质如何在结构上重新配置以响应行星磁场的分子基础，通过对单电子的量子效应进行转导，目前尚不清楚。在迁徙的鸣禽中，如欧洲知更鸟，隐花色素4（Cry 4）是被鉴定为与磁感觉相关的蛋白质。Cry 4的光还原已被证明对体外磁场敏感。然而，很少有人知道Cry 4的结构和构象变化的地磁场。在这里，我们的目标是破译Cry 4蛋白的内部运作，作为候鸟对地球磁场的分子转换器。您将学习各种尖端和高度可转移的生物物理和计算工具和技术。该奖学金将提供一个难得的机会，成为氢/氘交换质谱（HDX-MS）的专家，使用由埃克塞特大学生命系统研究所的菲利普斯实验室开发的新型原型仪器。您将在磁刺激下对蛋白质结构动力学进行毫秒级时间分辨测量。然后，您将使用这些实验结果进行分子动力学模拟（Mulholland Group，Univ.布里斯托），并将其与量子力学计算（Kattnig Group，Univ.埃克塞特）相结合。因此，您将以原子分辨率制作Cry 4功能切换过程的实验驱动分子电影。

Birds, fruit flies and many other animals are equipped with the remarkable ability to sense the Earth's magnetic field by means of a biochemical reaction in cryptochrome proteins. Surprisingly, this protein molecular compass utilises truly quantum effects to respond to changes in the magnetic field as the animal navigates. The molecular basis of how these proteins structurally reconfigure in response to planetary magnetic fields, transduced by quantum effects on single electrons, is unknown. In migratory songbirds, such as the European robin, Cryptochrome 4 (Cry4) is the protein identified to correlate with magnetosensation. Photoreduction of Cry4 has been shown to be sensitive to magnetic fields in vitro. Yet, little is known about the structure of Cry4 and which conformational changes transduce the geomagnetic field. Here, we will aim to decipher the inner workings of Cry4 protein as the molecular transducer of our planet's magnetic field by migratory birds. You will learn a variety of cutting-edge and highly transferable biophysical and computational tools and techniques. This studentship will provide a rare opportunity to become an expert in hydrogen/deuterium exchange mass spectrometry (HDX-MS), using novel prototype instrumentation developed by the Phillips lab at The Living Systems Institute, Univ. Exeter. You will make millisecond time-resolved measurements of the protein structural dynamics under magnetic stimulation. You will then use these experimental results to seed molecular dynamics simulations (Mulholland Group, Univ. Bristol) and combine this with quantum mechanics calculations (Kattnig Group, Univ. Exeter). As a result, you will produce an experimentally driven molecular movie of the process of Cry4 functional switching with atomistic resolution.