Association-induced conformational switching in biomolecules studied by Molecular Dynamics simulations (B02)

分子动力学（MD）模拟允许人们在原子分辨率上研究生物分子结合和相关构象变化。我们将应用md模拟和先进的采样技术来了解几个模型系统的构象转换过程的分子细节，其中大多数在CRC1035中进行了实验研究。这将包括DNA结合区域在与DNA结合时从部分未展开状态到折叠状态的转变，白细胞介素il - 23α中无序片段在与il - 12β结合形成功能性il - 23复合物时的折叠转变，以及翻译后修饰如何调节GTPase蛋白的构象转换。实验结构数据将有助于启动和指导模拟研究。

Molecular Dynamics (MD) simulations allow one to study biomolecular binding and associated conformational changes at atomic resolution. We will apply MD-simulations and advanced sampling techniques to understand the molecular details of conformational switching processes on several model systems most of which are studied experimentally in the CRC1035. This will include the transition of a DNA-binding domain from a partially unfolded state to a folded state upon binding to DNA, folding transitions of disordered segments in the interleukin IL23α upon association with IL12β to form a functional IL23 complex and how post-translational modification can modulate conformational switching in GTPase proteins. Experimental structural data will help to start and guide the simulation studies.