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Projects 2005

Sponsoring Laboratory/Section:

Laboratory of Chemical Physics, Ultrafast Biophysical Chemistry Section
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Section Chief/Mentor:

Philip Anfinrud, Ph.D.
e-mail: anfinrud@helix.nih.gov
Phone: 301-435-6034
Fax: 301-435-6710

Laboratory Description and Project area:

DNA is the blueprint of life, but proteins are the molecules that make life “happen.” The field of structural biology has shown us what many of these life-giving molecules look like, but their structures alone don’t tell us how they work at the molecular level.

To generate a deeper understanding of how proteins function, we are developing cutting edge experimental methods to watch a protein as it executes its designed task. Knowledge of “how” a protein functions would empower scientists to develop drugs whose function is specifically tailored from the chemical point of view. To develop a molecular level understanding of protein function, we use “pump-probe” time-resolved spectroscopy and crystallography to watch proteins as they move. The time resolution achieved is around ~100 fs (10-13 sec) with spectroscopy and ~100 ps (10-10 sec) with crystallography. In either case, a laser “pump” pulse of < 100 fs duration is used to trigger a photophysical or photochemical reaction and a delayed “probe” pulse is used to measure the spectral or structural evolution of the protein. In essence, this pump-probe technique provides us with a means to acquire “snapshots” of a protein as it executes its designed function.

By monitoring the changes that occur over time, we aim to develop a foundation for understanding how proteins execute their designed tasks with such high efficiency and selectivity. In preparation for time-resolved crystallography experiments, we need to characterize the static and transient absorbance spectrum of representative protein crystals. Former BESIP summer students have helped assemble and test a home-built micro-focusing spectrometer capable of recording polarized absorbance spectra of protein crystals as small as a few tens of microns in diameter.

In 2005, a summer intern would have the opportunity to further extend the capabilities of this instrument so that it can be used to pursue time resolved studies of protein crystals with long-lived intermediate states. Upon demonstrating proficiency using this spectrometer, the summer intern would have the opportunity to participate in ultrafast time-resolved studies of these crystals using a cutting edge transient absorbance spectrometer. An intern engaged in this protein biophysics research project would develop technical skills in optics, spectroscopy, LabVIEW computer programming, lasers, ultrafast time-resolved methods, and the handling of micron-scale crystalline protein samples.