All projects were supported in part by grants from 
the Pittsburgh supercomputer center (funded by 
the National Science Foundation and the National 
Institutes of Health) . 
Dr. Briinger is also Associate Professor of Mo- 
lecular Biophysics and Biochemistry at Yale 
University. 
Books and Chapters of Books 
Briinger, A.T. 1 99 1 . A unified approach to crystal- 
lographic refinement and molecular replace- 
ment. In Crystallographic Computing 5. From 
Chemistry to Biology (Moras, D., Podjarny, A.D., 
and Thierry, J.C., Eds ). Oxford: Oxford Univer- 
sity Press, pp 392-408. 
Habazettl, J., Nilges, M., Oschkinat, H., Briinger, 
A.T., and Holak, T.A. 1991. NMR structures of 
proteins using stereospecific assignments and re- 
laxation matrix refinement in a hybrid method of 
distance geometry and simulated annealing. In 
Computational Aspects of the Study of Biologi- 
cal Macromolecules by Nuclear Magnetic Reso- 
nance Spectroscopy (Hoch, J., Ed.). New York: 
Plenum, pp 395-408. 
Nilges, M., Kuszewski, J., and Briinger, A.T. 1991 . 
Sampling properties of simulated annealing and 
distance geometry. In Computational Aspects of 
the Study of Biological Macromolecules by Nu- 
clear Magnetic Resonance Spectroscopy (Hoch, 
J., Ed.). New York: Plenum, pp 451-455. 
Articles 
Briinger, A.T. 1991. Recent developments in crys- 
tallographic phasing and refinement of macromol- 
ecules. Curr Opin Struct Biol 1:1016-1022. 
Briinger, A.T. 1992. The free R-factor: a novel sta- 
tistical quantity for assessing the accuracy of crys- 
tal structures. Nature 355:472-474. 
Kuszewski, J., Nilges, M., and Briinger, A.T. 1992. 
Sampling and efficiency of metric matrix distance 
geometry: a novel partial metrization algorithm./ 
BiomolNMR 2:33-56. 
Simonson, T., Perahia, D., Bricogne, G., and 
Briinger, A.T. 1991. Dielectric properties of 
proteins: microscopic and macroscopic theory. / 
Chim Phys 88:2701-2708. 
Treutlein, H., Schulten, K., Briinger, A.T., Kar- 
plus, M., Deisenhofer, J., and Michel, H. 1992. 
Chromophore-protein interactions and the func- 
tion of the photosynthetic reaction center: a mo- 
lecular dynamics study. Proc Natl Acad Set USA 
89:75-79. 
White, S.A., Nilges, M., Huang, A., Briinger, A.T., 
and Moore, P.B. 1992. An NMR analysis of helix I 
from the 5S RNA of Escherichia coli. Biochemis- 
try 31:1610-1621. 
BIOPHYSICAL STUDIES OF EUKARYOTIC GENE REGULATION 
AND MOLECULAR RECOGNITION 
Stephen K. Burley, M.D., D.Phil., Assistant Investigator 
Dr. Burley's laboratory is studying the problem of 
molecular recognition in biological systems. The in- 
vestigations are aimed at developing a detailed un- 
derstanding of the physical principles that govern 
molecular recognition. Through x-ray crystallogra- 
phy and other biophysical techniques. Dr. Burley 
and his colleagues determine and characterize the 
three-dimensional structures of biological macro- 
molecules and their complexes with DNA, proteins, 
or other ligands. Thus a wealth of atomic detail is 
available for analysis, using biochemical, molecular 
genetic, and theoretical methods to provide a func- 
tional description of the intra- and intermolecular 
interactions responsible for stabilizing macromolec- 
ular complexes and thereby mediating molecular 
recognition. 
The proteins, or transcription factors, involved in 
regulating levels of eukaryotic gene expression pro- 
vide useful model systems for studying the mecha- 
nism (s) by which a protein can recognize a specific 
region of DNA. In addition, the transcriptional con- 
trol machinery is a good source of model systems for 
protein-protein recognition, which also occurs rou- 
tinely during transcription of genes in eukaryotes. 
Dr. Burley's laboratory has been combining x-ray 
crystallographic structure determinations of tran- 
scription factor-DNA complexes with biophysical 
characterization of these protein-nucleic acid 
assemblies. 
Crystal Structure of TATA-Box Binding Protein 
In collaboration with Drs. Robert G. Roeder and 
Nam-Hai Chua (Rockefeller University), Dr. Burley 
and his co-workers are studying the three- 
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