Structural Biology at NIH - Optical spectroscopy and physical methods

* Senior Investigator: V. Adrian Parsegian

* Affiliation: Laboratory of Structural Biology, DCRT and Section on Molecular Forces & Assembly, NIDDK.

* Research: Direct measurement and theory of forces between macromolecules in molecular assemblies; protein conformation in solution and in membranes.

* DNA-DNA interactions, protein/DNA organization.

* Measurement of protein interactions, especially fibrous proteins such as collagen, to develop potentials to apply to folding, assembly, and allosterism.

* Ion-transport proteins reconstituted into bilayer membranes; allosteric proteins in solution. Recent work has succeeded in changing conformation through the same techniques as used to move molecules in force/distance measurements.

* Formulation and computation of intermolecular forces.

* Personnel/Resources: Donald C. Rau (physical biochemistry, electrical and circular dichroism, x-ray diffraction, osmotic stress); Nina Sidorova (physical biochemistry); Sergey Leikin (x-ray diffraction, osmotic stress, theoretical physics); Sergey Bezrukov (channel reconstitution, "noise" analysis of dynamics); Rafik Brutyan (channel reconstitution); Rudi Podgornik (x-ray diffraction, statistical mechanics).

For its measurements of intermolecular forces, the group has a fixed-anode x-ray source, osmometers for applied osmotic stress, and locally developed software for reading and analyzing films of x-ray scattering. The group also has several electrical optical spectrometers of advanced design and two fully developed bilayer membrane channel "rigs" with optimal noise/isolation features and electronics to monitor high speed channel dynamics and kinetics.

* Publications:

S. Leikin, V.A. Parsegian, D.C. Rau, & R.P. Rand (1993). Annual Review Phys. Chem 44:369-395. Hydration forces.

S.M. Bezrukov, & J.J. Kasianowicz (1993). Physical Review Letters 70:2352-2355. Fluctuations in current through a single open ion channel reveal titration kinetics of ionizable residues.

M.F. Colombo, D.C. Rau, & V.A. Parsegian (1992). Science 256:655-659. Protein solvation in allosteric regulation: a water effect on hemoglobin.

D.C. Rau, & V.A. Parsegian (1992). Biophys. J. 61:246-271. Direct measurement of intermolecular forces between counterion-condensed DNA double helices.

* Contact: Dr. V.A. Parsegian, Bldg. 12A, Room 2041 or Bldg. 5, Room 405. DCRT, NIH, Bethesda, MD 20892.

Tel: (301) 402-4698 or 496-1121 Fax: (301) 496-2172

E-mail: VAP@CU.NIH.GOV