GENOMICS: Protein Function [was: Re: *sox18* in the bag]

From: Robert Bradbury (
Date: Wed Mar 29 2000 - 09:06:45 MST

Hal discussed that "the protein problem is not understood".
John commented "you can find its shape with X ray diffraction or NMR".

I'll offer several comments as to why this will move fast.
1) It is recognized that you will have lots of gene sequences to
   which you will want the actual structure. Scientists involved
   in this field (as documented in Science), are moving towards
   an assembly line approach (as was done with sequencing), to
   allow much, much faster throughput for crystalization and
   X-ray diffraction or NMR. Still, there will be some proteins
   for which you cannot get crystals.
2) Computer modeling of the protein shape, based on first principles,
   known shapes of protein "motifs" (that have been copied throughout
   the genomes), and expanded computer power (e.g. IBM's Blue Gene)
   will converge to give highly accurate models for those proteins
   that for which crystals are difficult, and even those for which
   they are easy.
3) We will rapidly determine genes involved in specific pathways (through
   evolutionary conservation across organisms), the regulatory sequences
   for genes (which must be conserved across organisms as well) and the
   pathways in which they function (through differential expression studies).
   Knowing what genes stay together and play together, combined with
   computer analysis of the 3-D substructures that identify conserved
   regions, catalytic sites, phosphorylated amino acids, etc. will
   allow rapid assignment of functions.
4) Much of the genome is involved in developmental processes and therefore
   can be left to "cleanup" efforts and/or those interested in basic
   biology or birth defects.

All of this implies that within a few years, we should have identified
the pathways and genes and functions responsible for the major diseases
and pathologies. Some solutions will be easy, and others will be difficult.
But once the problems are identified, clever people can identify
multiple possible targets and work on them until solutions are found.

So, I think over the next ten years people will be quite surprised
at how fast things will move.


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