NESG Newsletter
March 2003
Welcome to the first NESGC newsletter. We will be presenting relevant reports
from various NESG groups on interesting topics, particularly in the following six
areas:
1) Progress in target selection
2) New technology development
3) New structures solved
4) Publications
5) Receipt of associated funding
6) Interesting news
We encourage you to send us your thoughts regarding the format of this
newsletter so that we can make it a truly valuable communication tool for
members of this consortium.
Please send your comments and/or contributions for the next April NESG
Newsletter to: mailto:cbiamonti@hotmail.com
New NESG Structure Gallery
Nat Echols in Mark Gerstein's group has done a beautiful job of redesigning the
NESG Structure Gallery
http://www.nesg.org/index.pl?Structures
Deyou Zheng at CABM, Rutgers maintains a complete collection of the NESG
structure coordinate files which are shown as ribbon diagrams in the Structure
Gallery.
The NESG Structure Gallery provides links to PDB and BMRB files, as well as to
NESG Structure Validation Reports and the corresponding SPiNe Target
Record. For structures deposited in the PDB, all the information in the SPiNe
about the corresponding sample production, purification, and characterization is
also open to the public without a password. The Structure Gallery will soon also
be linked to Structure and Function Annotation Pages that are being prepared by
Sharon Goldsmith in Barry Honig's lab, and to other bioinformatics resources
being developed in the Murray and Rost labs.
PSI Advisory Committee Recommends Supplemental Funding
for Functional Studies
The report of the PSI Advisory Committee (PSIAC) on the Nov. 14-15
Executive Meeting at NIH has been posted on the NIGMS web site at
http://www.nigms.nih.gov/news/reports/psi_advisory02.html
The report summarizes the recommendations of the PSIAC in several areas,
including:
1. Better Communication with Scientific Community
2. Laboratory Information Management
3. Structure vs. Function
4. How Many Production Groups in Next Phase of PSI
5. Ongoing Technology Developments
Some key conclusions of the report are:
- Supplemental funding (up to $50K per collaboration) is now available for followon studies of biochemical function. Contact G. Montelione for details.
- LIMS are viewed as critical to the infrastructure for these projects.
- Although the plans for the next phase of the PSI are not yet disclosed, it will
include significant support for continued technology development.
Eleven NESG Structures Submitted to PDB In February
According to SPINE, there are now 39 NMR structures and 32 X-ray crystals
structures determinate by the NESG Consortium. Of these 71 structures, 64
have been submitted to the PDB. In 2003, 15 structures have been submitted to
the PDB.
The following eleven protein structures were submitted by the NESG Consortium
to the PDB in February 2003:
YTYst425
TT87
ER82
ER115
IR73
SR127
JR19
OP3
QR6
GR2
IR63
New Eukaryotic NESG Target Proteins
Jinfeng Liu and Burkhard Rost recently provided an additional set of some 2240
full length protein targets from Arabidopsis thaliana, which have been entered in
ZebaView and SpiNe. These are now in production together with our other
eukaryotic targets:
Caenorhabditis elegans: 337
Drosophila melanogaster: 252
Homo sapiens: 2839
Saccharomyces cerevisiae: 583
In addition, there are some 3000 prokaryotic protein targets.
Progress Report from John Cort, PNNL
Target selection:
QR62 buffer being optimized by Yiwen Chang and Rajan at Rutgers.
Two new samples, ZR31 or HR319 has been chosen for isotope enrichment and
structure analysis by NMR.
New structures solved:
NESG target OP3, Vibrio cholerae protein VC0424 has been submitted to the
PDB (1NXI, 2/10/03).
NESG target YTYst425. This structure is a new fold. Also the protein is unique to
S. cerevisiae, except for a moderately similar homolog in S. pombe.
Structural statistics are provided in accompanying Excel spreadsheet,
nesg_march03_structures.
Collaborations:
We are collaborating with Sharon Goldsmith in Barry Honig’s lab to perform the
structural and functional analysis of VC0424. Some of her analysis is available
at:
http://trantor.bioc.columbia.edu/sharon/Target_list_1.html
(use the spine login and password).
These structural and functional annotation will soon be linked to SPiNe and to the
NESG Structure Gallery. Sharon has done analysis with ConSurf and
comparisons with ACT and RAM domains which have similar folds and known
active site residues. VC0424 does not appear to be related to these domains.
Janet Huang at Rutgers was extremely helpful in performing AutoStructure
calculations on VC0424. We used AutoStructure and our preliminary structure
along with manually-derived restraints to find over 160 new medium and long
range restraints. We then used these in the X-PLOR calculation using the XplorNIH software.
Publications:
“Solution structure of the yeast ubiquitin-like modifier protein Hub1”, T.A.
Ramelot, J.R. Cort, A.A. Yee, A. Semesi, A.M. Edwards, C.H. Arrowsmith, M.A,
Kennedy, 2003, J. Struct. Funct. Genom., in press.
Progress in Robotic Crystal Mounting
This project is directed by Prof. Peter Allen at Columbia and is aimed at using
computer vision and robotic grasping to mount protein crystals automatically.
Computer Vision can provide rich knowledge about the spatial arrangement of
objects to be manipulated as well as knowledge about the means of
manipulation, which in our case are the instruments needed to perform crystal
mounting. Our goal is to visually monitor and control these instruments as they
isolate and mount protein crystals. We have developed an integrated visual
control system, consisting of a high-resolution optical microscope, digital imaging
system, image based servo-controllers and a micromanipulator that is able to
precisely position a grasping loop with respect to a protein. The visual tracking
algorithms use uncalibrated methods, making the system simple to use and
robust. Once a crystal is acquired in an image, the tracking system can position
the grasping loop to within 1 pixel of the centroid of the crystal, which
corresponds to a positioning accuracy of .1 micrometers (Mezouar & Allen,
2002). We are currently investigating more advanced grippers, including silicon
micro-machined tweezers, to pick up the crystals automatically.
Mezouar, Youcef and Peter K. Allen Visual servoed micropositioning for protein
manipulation, Int. Conf. Intelligent Robots and Sytems (IROS 2002), Lausanne,
Switzerland, Oct. 1-3, 2002.
Columbia Crystallography Group Completes Seven New Crystal
Structures
The following structures have been solved by X-ray crystallography and statistics
are provided in the accompanying Excel file, nesg_march03_structures:
ER82
ER24
IR73
ER13
SR127
IR63
SR144
Recent Publications by Burkhard Rost Bioinformatics Group,
Columbia University
1. J Liu & B Rost (2002) Target space for structural genomics revisited.
Bioinformatics, 18, 922-933.
2. CP Chen, A Kernytsky & B Rost (2002) Transmembrane helix predictions
revisited. Prot Science 11, 2774-2791.
3. CP Chen & B Rost (2002) Long membrane helices and short loops predicted
less accurately. Prot Science 11, 2766-2773.
4. R Nair & B Rost (2002) Sequence conserved for sub-cellular localization. Prot
Science 11, 2836-2847.
5. Y Ofran & B Rost (2003) Analysing six types of protein-protein interfaces. J
Mol Biol 325, 377-387.
6. CAF Andersen & B Rost (2003) Automatic secondary structure assignment. In
'Structural bioinformatics' P Bourne & H Weissig (eds.), John Wiley, 339-361.
7. B Rost (2003) Prediction in 1D: secondary structure, transmembrane helices
and accessibility. In 'Structural bioinformatics' P Bourne & H Weissig (eds.), John
Wiley, 557-585.
8. P Carter, J Liu & B Rost (2003) PEP: Predictions for entire proteomes. Nucl
Acids Res 31, 410-413.
9. R Nair, P Carter & B Rost (2003) NLSdb: database of nuclear localization
signals. Nucl Acids Res 31, 397-399.
10. J Liu & B Rost (2003) Domains, motifs, and clusters in the protein universe.
Curr Opin Chem Biol 7, 5-11.
11. B Rost (2003) Rising accuracy of protein secondary structure prediction. In
'Protein structure determination, analysis, and modeling for drug discovery', D
Chasman (ed.), Dekker, New York, 207-249.
Publications in press
12. B Rost (2003) Neural networks predict protein structure: hype or hit? In
'Artificial intelligence and heuristic methods for bioinformatics' P Frasconi (ed.),
IOS Press, in press.
13. R Zidovetzki, B Rost, Don L Armstrong & I Pecht (2002) Transmembrane
domains in the functions of Fc receptors. J Biophysical Chemistry in press.
14. KO Wrzeszczynski & B Rost (2003) Cataloguing proteins in cell cycle control.
In 'Cell cycle checkpoint control protocols' H Lieberman (ed.).
15. B Rost, J Liu, D Przybylski, R Nair, H Bigelow, K Wrzeszczynski & Y Ofran
(2003) Predicting protein structure through evolution. In 'Chemoinformatics From Data to Knowledge' J Gasteiger & T Engel (eds.), Wiley.