US-Sweden Cooperative Science: Protein-Nucleic Acid Interactions and Dynamics

该奖项将支持罗切斯特大学医学院的Thomas M. Nordlund教授和斯德哥尔摩卡罗林斯卡研究所的Rudolf Rigler博士在分子动力学领域的合作研究。特别是，通过直接实验和计算机模拟，将研究分子运动对Eco R1蛋白结合和溶解DNA的影响。实验将使用极快的光电倍增管来计算正在研究的分子附近的分子的荧光发出的光子；这种荧光发生在结合或解体过程中。分子的激发将由激光和同步辐射进行；后者具有连续可调的优点，便于测量荧光发射的时间依赖性。计算机模拟将包括计算在结合和溶解过程中产生的各种蛋白质- dna反应的能量函数之间的相关性。激光和同步加速器实验设备的可用性以及计算机模拟的专家人员使卡罗林斯卡研究所成为这项合作研究的理想场所。这项工作将为美国研究者提供一个使用他通常无法使用的设备和技术的机会，并学习专门的技术，以便在他自己的机构中应用。此外，该项目将增加我们对DNA如何通过与各种蛋白质的相互作用进行修饰的理解，这可能会导致许多实际应用。

This award will support collaborative research between Professor Thomas M. Nordlund of the University of Rochester School of Medicine and Dr. Rudolf Rigler of the Karolinska Institute, Stockholm in the field of molecular dynamics. In particular, the influence of molecular motions on the binding and dissolution of DNA by the Eco R1 protein will be studied, both through direct experimentation and using computer simulation. The experiments will use an extremely fast photomultiplier to count the photons emitted by the fluorescence of a molecule adjacent to that whose motions are being studied; this fluorescence occurs during binding or disintegration. Molecular excitation will be performed by both laser and synchrotron radiation; the latter has the advantage of continuous tunability and facilities for measuring the time dependence of the fluorescence emission. The computer simulations will involve calculating correlations among energy functions for the various protein-DNA reactions which arise in the binding and dissolution process. The availability of both laser and synchrotron experimental apparatus and expert staff for the computer simulations makes the Karolinska Institute an ideal location for this collaborative research. This work will provide the U.S. investigator with an opportunity to use equipment and techniques to which he does not ordinarily have access, and to learn specialized techniques for subsequent application at his own institution. In addition, the project will increase our understanding of how DNA is modified by interactions with various proteins, which may lead to numerous practical applications.