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.
