The Organic and Macromolecular Chemistry Program in the Division of Chemistry and the Europe and Eurasia Program in the Office of International Science and Engineering will support the collaborative research program of Professors Nikolai Strynnikov of Purdue University and Bernd Reif of the Leibniz-Institute for Molecular Pharmacology in Germany. This award coordinates with a collaborative award funded by the Deutsche Forschungsgemeinschaft (DFG). The collaboration seeks to compare and ultimately combine the dynamics data from solution- and solid-state NMR experiments. Substantial evidence exists that many forms of internal motion do not change significantly upon transition from solution to solid ('similarity hypothesis'). For instance, side chains sequestered in the protein hydrophobic core are likely to show similar dynamic behavior. The spectroscopic context, on the other hand, is different: solid data are broadly sensitive to internal dynamics in the picoseconds (ps) to nanoseconds (ns) time frame, whereas the solution relaxation rates are sensitive only to those motions that are faster than molecular tumbling. The combination of the two complementary spectroscopic perspectives can provide a unique insight into protein dynamics. The research will follow a two-step scheme. First, the investigators are planning to focus on side-chain methyl groups. Spin-lattice relaxation in methyls is dominated by the internal dynamics (fast methyl spinning) in solids and solutions alike. This type of data offers, therefore, a convenient opportunity to draw a direct comparison between the two samples. Based on the methyl data, the investigators plan to establish support for their 'similarity hypothesis'. In the second stage of the project, the benefits of the similarity will be exploited. Specifically, backbone 15N relaxation data will be analyzed in a combined fashion by fitting simultaneously the solution- and solid-state relaxation rates. It is anticipated that a separation of the picosecond and nanosecond dynamics can be achieved along these lines, leading to a new level of detail in the description of protein motions. The similarity paradigm can be extended to many NMR experiments and to protein systems of general biophysical significance.
The Organic and Macromolecular Chemistry Program in the Division of Chemistry and the Europe and Eurasia Program in the Office of International Science and Engineering support the joint collaboration between Professors Nikolai Strynnikov of Purdue University and Bernd Reif of the Leibniz-Institute for Molecular Pharmacology in Germany who will employ solution- and solid-state NMR to study biomolecular dynamics. The integration of the two approaches can potentially have an impact across the entire field of protein science. The resulting progress can facilitate the transition from static to dynamic protein models in quintessential applications such as rational drug design and biotechnology. The exchange visits between the US and the German laboratories will broaden the scientific horizons of the students involved. To further increase the students' exposure to international science, visits to the leading national research institutions will be organized by the receiving side. The US principal investigator will join the German PI to organize a special session at the annual European Summer School on solid-state NMR dedicated to the area 'where solid meets solution'. One young US scientist (at the graduate student or postdoctoral level) who made a significant contribution in this area will be identified and given an opportunity to present his/her work at this meeting. The pulse sequences and computer programs written as a result of the proposed research will be made available to the broad NMR community through the participants' websites.
