SCIENCE AT THE EDGE SEMINAR
http://www.pa.msu.edu/seminars/edge/

11:30 A.M., Friday, September 27, 2002
Room 1400 Biomedical and Physical Sciences Building
Refreshments served at 11:15


Title:
   Comparative Protein Structure Modeling of Genes and Genomes

Speaker:
   Andrej  Sali
   Laboratory of Molecular Biophysics
   The Rockefeller University, New York, NY

Abstract:
Structural genomics aims to determine or accurately predict 3D structure of
most proteins (1). This aim will be achieved by a focused, large-scale
determination of protein structures by X-ray crystallography and NMR
spectroscopy, combined efficiently with accurate protein structure
prediction (2). Comparative protein structure modeling will be discussed in
this context. To allow large-scale modeling, we automated fold assignment,
sequence-structure alignment, comparative model building, and model
evaluation (3). These steps were implemented mostly in our MODELLER package,
which is available on the web at http://guitar.rockefeller.edu/. The
modeling pipeline has been applied to all of the approximately 750,000
protein sequences in the TrEMBL database, resulting in models for segments
of approximately 430,000 proteins. These models are stored in the MODBASE
database (4), accessible over the web at http://guitar.rockefeller.edu/modbase.
Several examples of how comparative modeling can be useful in the biological
analysis of individual proteins as well as whole genomes will be described.


References:

R. Sanchez, U. Pieper, F. Melo, N. Eswar, M.A. Marti-Renom, M.S.
Madhusudhan, N. Mirkovic, and A. Sali. Protein structure modeling for
structural genomics. Nat. Struct. Biol. 7, 986-990, 2000.

D. Baker, A. Sali.  Protein structure prediction and structural genomics.
Science 294, 93-96, 2001.

R. Sanchez and A. Sali. Large-scale protein structure modeling of the
Saccharomyces cerevisiae genome. Proc. Natl. Acad. Sci. USA 95, 13597-13602,
1998.

U. Pieper, N. Eswar,  A.C. Stuart, V.A. Ilyin, A. Sali. MODBASE, a database
of annotated comparative protein structure models. Nucleic Acids Research
30, 255-259, 2002.