Re: [ccp4bb]: Improving data processing with Gaussian blur

[Derek Logan <derek.logan@mbfys.lu.se>]

On Tuesday, April 1, 2003, at 06:06 PM, Bernhard Rupp wrote:

> It is also known that Photoshop is the most
> effective density modification program available....
> It is believed that together with combinatorial
> data generation and phases from predicion models it
> willreplace CCP4 with the next few years.
>  
> Adobe Xtallator...

Whether your space is real or reciprocal, your source code should be open! Use Gimp instead!

BTW I found this in an old Hampton Research newsletter. Were our colleagues ever sccessful in patenting bioinformatics, structural genomics and structure-based drug design in one fell swoop?

Derek

PROCESS FOR PAN-GENOMIC DETERMINATION OF MACROMOLECULAR ATOMIC STRUCTURES  

APL   08-08-02   20020107643  NDN- 223-0121-8183-2 
INVENTOR(S)- HENDRICKSON, WAYNE A.; HONIG, BARRY    
2002-08-08    
PATENT APPLICATION NUMBER- 235986/09    
DATE FILED- 1999-01-22    
PUBLICATION NUMBER- 20020107643 A1     
U.S. PATENT CLASS- 702027000O; X702019000; X422068100    
INTERNATIONAL PATENT CLASS- G06F01900; G01N03348; G01N01506    

A process for pan-genomic determination of three-dimensional macromolecular
atomic structures uses a unique combination of components. All known
structural information, sequence information and functional information are
systematically organized into a genomics database. Advanced tools of
bioinformatics are used to cluster all known gene products into families of
homologous sequences. Simultaneously, in parallel for each such family, a
few cDNAs from appropriately representatives species are cloned into
expression vectors for a few expressions systems. Constructs are then
screened for expression, and those that are effective advance to the
preparative step. Expressed proteins are prepared, purified and
characterized. Purified proteins are set to crystallize in parallel against
crystallization screens. Crystals that grow are tested for suitable
diffraction characteristics. A suitable crystal is frozen, and diffraction
data are measured using the multiwavelength anomalous diffraction (MAD)
method at a synchrotron which uses undulator beamlines for high-throughput
crystallography. Diffraction data are analyzed by the MAD phasing method,
an atomic model is built, and the model is refined against the diffraction
data. The refined model is analyzed in the context of (1) sequence
information from other family members, (2) all other known 3D structures,
and (3) functional motifs. It is also analyzed for surface characteristics
with the aim to define active sites and macromolecular contact sites. For
relevant structures, the active site properties are used to define classes
of compounds predicted to have binding potency. Computational tools for
homology model building are used to develop models for homologs. The
homology models may be used in target selection, drug design, or design of
more appropriate constructs for experimental analysis. The ensemble of all
known structures is used to further advance the effectiveness of the
bioinformatics tools.    
EXEMPLARY CLAIMS- What is claimed is: 1: A system for pan-genomic
determination of three-dimensional macromolecular atomic structures,
comprising: database means for systematically organizing all known
structural information into a genomics database of structural information,
sequence information and functional information; bioinformatics means for
using said structural information, sequence information and functional
information stored in said database to cluster a plurality of known gene
products into a plurality of families of homologous sequences; protein
synthesis means for synthesizing for each family, in parallel
simultaneously, a plurality of member proteins using genomics information
of a plurality of appropriately representative species; screening means for
screening the synthesized proteins to determine ones that are effective;
protein processing means for preparing, purifying and characterizing the
screened proteins determined to be effective by said screening means;
crystallization means for crystallizing a plurality of the purified
proteins in parallel against a plurality of crystallization screens, and
testing a plurality of grown crystals for predetermined diffraction
characteristics to determine suitable ones of said plurality of grown
crystals; X-ray crystallography means for performing high-throughput
crystallography, said X-ray crystallography means having diffraction
measuring means for measuring a suitable crystal for diffraction data,
analyzing means for analyzing said diffraction data, means for building an
atomic model, and means for refining said model against said diffraction
data and storing the refined model in said database; structure extraction
means having means for analyzing the refined model using sequence
information of other family members and information of other known
three-dimensional structures, means for analyzing for functional motifs and
for surface characteristics to define active sites and macromolecular
contact sites, and means for defining at least one class of compounds
predicted to have binding potency using the active sites information; and
homology model building means for developing a homology model using an
atomic model retrieved from said database, wherein an ensemble of all known
structures is used to further advance an effectiveness of said
bioinformatics means.