NMR – The movie

Ten construction workers will often get a job done faster than one. But in digging a deep well, for instance, ten workers are a waste of human resources: the diggers can’t work simultaneously, as the second worker isn’t able to start digging until the first one has finished, and so on.

A similar challenge is encountered by scientists who study the structure and dynamics of molecules using nuclear magnetic resonance (NMR) spectroscopy. This technique serves as an essential tool in understanding numerous molecules – including proteins, nucleic acids and active pharmaceuticals – in their natural surroundings. It does this by exposing them to electromagnetic radiation and studying the dispersion patterns of the electromagnetic waves that hit the molecules. However, to obtain a full NMR picture of such complex molecules one needs to perform numerous measurements that are based on the same “serial” principle as well digging: hundreds or thousands of one-dimensional scans need to be performed one after the other; these scans need then to be combined to create a unified multidimensional picture of the molecule. While a single scan may take a fraction of a second, multidimensional procedures may last several hours or even days.

A team led by Prof. Lucio Frydman of the Weizmann Institute’s Chemical Physics Department has now found a way to perform multidimensional NMR with a single scan. The new method, described in the December 2002 issue of the Proceedings of the National Academy of Sciences USA (PNAS), is expected to significantly speed up molecular studies routinely performed in diverse fields.

The method “slices” a sample into numerous thin slices and then simultaneously performs all the measurements required by multidimensional NMR – lasting a fraction of a second each – on every one of these slices. The system then integrates all the measurements according to their precise location, generating an image that amounts to a multi-dimensional spectrum from the entire sample. Essentially, Prof. Frydman has found a way to allow NMR “well diggers” to work simultaneously.

Scientists will now be able to observe rapid changes taking place in molecules, such as the folding of proteins. In this sense, the new method developed by Prof. Frydman amounts to a transition from taking still “NMR photos” to recording “NMR movies.”

Prof. Frydman’s method may also have a great impact on the design of new drugs and the development of catalysts, particularly in the emerging fields of combinatorial chemistry and of metabonomics.

Contributing to this research were Dr. Adonis Lupulescu of the Chemical Physics Department and Dr. Tali Scherf of Chemical Services at the Weizmann Institute of Science.

Prof. Lucio Frydman’s research is supported by the Abraham and Sonia Rochlin Foundation, the Henri Gutwirth Fund for Research, the Philip M. Klutznick Fund, the late Ilse Katz, Switzerland, and Minerva Stiftung Gesellschaft fuer die Forschung m.b.H.