Laser Techniques Reveal Molecular Folding

Reporting in the Feb. 20 issue of Science, scientists in the Timothy S. Zwier group at Purdue University in West Lafayette, Ind., have described how they used spectroscopic methods based on stimulated emission pumping to probe the folding process of tryptamine, a close analogue of the neurotransmitter serotonin and of the amino acid tryptophan. They hope that the approaches will enable a better understanding of conformational dynamics in proteins.

In the techniques, a UV dye laser pump excites a single conformation of the molecule to the zero-point vibrational level of the first excited electronic state, and a similar dump laser stimulates it back into a specific vibrational level in the ground electronic state. The sample then is collisionally cooled, and a third UV dye laser determines into which conformational minimum the sample has fallen by laser-induced fluorescence.

Tryptamine, for example, has seven conformational minima that are separated from one another by energy barriers, indicated by the red "valleys" in the image. By tuning the dump laser, the energy thresholds for isomerization from one minimum into other minima can be determined with high accuracy, and the proper choice of dump wavelength enables the selective formation of certain conformations of the molecule over others.