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，通过隐花色素蛋白的生化反应来感知地球磁场。令人惊讶的是，这种蛋白质分子指南针利用真正的量子效应来响应动物导航时磁场的变化。这些蛋白质如何在响应行星磁场的分子基础上重新配置结构，由单电子的量子效应转导，是未知的。在迁徙的鸣禽中，如欧洲知更鸟，隐花色素4 （Cry4）是一种与磁感相关的蛋白质。体外研究表明，Cry4的光还原反应对磁场敏感。然而，人们对Cry4的结构知之甚少，也不知道是哪些构象变化导致了地磁场。在这里，我们的目标是通过候鸟来破译Cry4蛋白作为地球磁场分子传感器的内部工作原理。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，让学生使用埃克塞特大学生命系统研究所菲利普斯实验室开发的新型原型仪器，成为氢/氘交换质谱（HDX-MS）专家。你将对磁刺激下的蛋白质结构动力学进行毫秒级的测量。然后，您将使用这些实验结果进行分子动力学模拟（Mulholland Group, university . Bristol），并将其与量子力学计算（Kattnig Group, university . Exeter）结合起来。因此，您将制作具有原子分辨率的Cry4功能开关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.