Opportunity at National Institute of Standards and Technology (NIST)
High-Resolution THz and Ultraviolet Laser Studies of Polypeptide Structure and Dynamics
Physical Measurement Laboratory, Quantum Electromagnetics Division
Please note: This Agency only participates in the February and August reviews.
|Plusquellic, David Francis
THz radiation interrogates the lowest frequency collective motions of biomolecular systems. These collective modes characterize the incipient motions for the large scale conformational changes along the torsional coordinates responsible for the flexibility of protein, polynucleotide, and polysaccharide backbones during folding and activation. The unique properties of this spectral region are evidenced by sensitivity to the (1) collective motions that extend across large portions of the biomolecular framework with length scales that extend over tens of angstroms, (2) protein/water interaction dynamics that occur on sub-ps timescales, and (3) an energy domain similar to the thermal energies required for biological activity. Furthermore, the THz region provides a sensitive probe of crystalline order, conformational form, peptide sequence, solvent interactions, H-bonding force constants, and anharmonic character of the force fields. In our lab, high-resolution, continuous-wave terahertz (THz) spectroscopy is used to measure the spectra of bulk (pellet) samples and aqueous samples over a wide range of temperatures as low as 1.6 K, We have also developed methods to enhance absorption sensitivity for oriented thin-film samples on waveguide interfaces. Quantum chemical (DFT/PW91) calculations performed on periodic solids in combination with gas-phase microwave data on numerous peptide mimetics have aided in characterizing the nuclear motions probed in the THz region and have elucidated some of the principal deficiencies in classical force field models like CHARMM. These calculations also help us to better understand the subtle balance that determines guest water absorption and conduction through the hydrophobic channels in peptides.
In a related research area, chirped pulse THz measurements are performed using amplifier/multiplier chains for excitation and sub-harmonic heterodyne receivers for detection of the absorption and free-induction decay spectra of gas phase molecules. Up to 6 different chirped pulse systems enable coverage from 90 GHz to near 1 THz for optimal access of quantum levels at thermally relevant energies. The systems are phase coherent and enable rapid (1 μs scans) and sensitive detection (ppb levels in a few minutes) in a multipass cell. Molecules and biomolecules are prepared in the gas phase using a slit jet nozzle or an effusive beam source. Fragmentation products may also be studied after passing the gas through a heated quartz pyrolysis source or following electric discharge in a pulse nozzle source.
Biophotonics; Photonics; Biomolecules; Cavity ringdown polarimetry; Classical molecular dynamics; CW THz spectroscopy; Folding dynamics; High-resolution continuous wave; Polypeptides; Proteins; Quantum chemical; Vibrational anharmonicity;
Open to U.S. citizens
Open to Postdoctoral applicants