X-ray crystallography is the main tool for determining protein structure. Since genomics is on the verge of creating a large number of proteins for structure determination, a corresponding large number of X-ray diffraction experiments will have to be performed. However, X-ray analysis is labor intensive so that the question of which protein crystal to choose for X-ray analysis from the vast pool of candidates becomes important from an economics standpoint. Therefore, it is desirable to have a rapid method to score protein crystals regarding their likelihood for being of diffraction quality. We propose to develop a method and apparatus for protein crystal scoring which is based on intrinsic fluorescence of proteins. Preliminary results obtained for three proteins demonstrated correlation between fluorescence spectra of single crystals and their internal order as determined by X-ray crystallography. During Phase I, we suggest to verify the hypothesis of correlation between fluorescence and diffraction properties on a large number of protein crystals. We anticipate that a rapid method for protein crystal scoring will be developed as a result of Phase I. In Phase II, the envisioned scoring method will be used as a core for building a prototype of an automated instrument which can be adapted for a variety of high throughput protein crystal growth technologies.

Proposed Commercial Applications

In the coming era of proteomics, the need for rapid assessment of protein crystals with respect to their ability to diffract X-rays will be enormous. At the present time, there is no method for rapid scoring of protein crystals. The envisioned fluorescence assay will fill the gap between high throughput crystallization technologies and labor intensive X-ray diffraction experiments and will provide researchers with a rapid and low cost technique for scoring protein crystals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM064095-01
Application #
6403963
Study Section
Special Emphasis Panel (ZRG1-SSS-6 (10))
Program Officer
Heath, Anne K
Project Start
2001-09-01
Project End
2002-05-31
Budget Start
2001-09-01
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$100,000
Indirect Cost
Name
Bioelectrospec, Inc.
Department
Type
DUNS #
158444724
City
Harrisburg
State
PA
Country
United States
Zip Code
17111