Dynamical aspects of molecular recognition and signal propagation in biomolecules

近几十年来，通过研究蛋白质的特定三维结构，人们对蛋白质的功能有了深刻的认识。伴随这一发展而来的是对以原子或近原子分辨率解析蛋白质和蛋白质复合物结构的方法的需求不断增加。一种同样通用的研究蛋白质动力学的方法才刚刚开始出现，并且可以预期获得与解决静态蛋白质结构的能力类似甚至更大的影响。在确定结构和动力学方面，物理逼真的计算机建模的作用必然会增加，因为它允许解释否则过于稀疏的实验数据。解析蛋白质结构最流行的技术是x射线晶体学、核磁共振（NMR）光谱学和电子显微镜。这些核磁共振是最通用的和独特的，在它的能力也探测蛋白质动力学在广泛的时间尺度上的原子分辨率。该项目的目的是开发计算工具，用于从实验数据中确定蛋白质结构和动力学，重点是核磁共振，并应用这些工具来研究构象转变和动力学在分子识别和信号转导中的作用。为了达到这些目标，我们将结合和发展结构预测、分子动力学模拟和统计力学领域的方法，并与实验组广泛合作。

Tremendous insight about protein function has been gained in recent decades by investigating their specific three dimensional structures. This development has been accompanied by an ever increasing demand for methods to resolve structures of proteins and protein complexes in atomic or near atomic resolution. An equally versatile methodology to investigate protein dynamics is only starting to emerge and can be expected to gain a similar or even greater impact as the ability to resolve static protein structures. The role of physically realistic computer modelling is bound to increase in both determination of structure and dynamics where it allows to interpret otherwise too sparse experimental data. The most popular techniques to resolve protein structures are X-ray crystallography, Nuclear Magnetic Resonance (NMR) Spectroscopy and electron microscopy. Of these NMR is the most versatile and unique in its ability to also probe protein dynamics in atomic resolution on a broad range of timescales. The aim of this project is to develop computational tools for determination of protein structures and dynamics from experimental data with the focus on NMR and to apply such tools to study the role of conformational transitions and dynamics in molecular recognition and signal transduction. To reach these goals we will combine and develop methodology in the fields structure prediction, molecular dynamics simulation and statistical mechanics and collaborate extensively with experimental groups.