Dynamical aspects of molecular recognition and signal propagation in biomolecules

近几十年来，通过研究蛋白质的三维结构，人们对蛋白质的功能有了深刻的认识。这种发展伴随着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不断增长的需求。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析静态蛋白质结构的能力相似甚至更大的影响。物理上逼真的计算机建模的作用必然会增加在结构和动力学的确定，它允许解释否则太稀疏的实验数据。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。其中NMR是最通用和独特的，它能够在广泛的时间尺度上以原子分辨率探测蛋白质动力学。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NMR，并应用这些工具来研究分子识别和信号转导中构象转变和动力学的作用。为了达到这些目标，我们将联合收割机和开发领域的结构预测，分子动力学模拟和统计力学的方法，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.