Proteomics; Just another name for biochemistry?
Dr Pamela Greenwell
Molecular and Medical Microbiology Research Group
School of Biosciences
University of Westminster
115, New Cavendish Street
London W1 W6UW.
The growth of the “omics” technologies has many people imaging we are just giving “sexy” names for
boring, old-fashioned technology. Who would dispute that genomics is just genetics and molecular biology, “glycomics”
is the study of glycosylation or that “metabolomics “ is simply the study of
metabolic pathways? Surely then, proteomics is just biochemistry. Indeed,
I have told my students that we are studying proteomics as they turn off at the
mere mention of the word biochemistry.
But is proteomics simply biochemistry?
The answer is a resounding NO! Proteomics
is a mixture of traditional biochemistry and the use of web based bioinformatics tools.
It enables us to understand and visualise protein structure, function, interaction and expression. This is really the traditional biochemistry aspect. However, in addition, it gives us the opportunity,
using bioinformatics, to predict the biochemical properties, structure and functions of proteins that have been derived from
translation of the cloned nucleotides or PCR products. Indeed, the output of
most genome projects has been random gene sequences whose function and identity has been derived using bioinformatics tools.
So what can I do? If we go to Genome Japan (http://www.genome.ad.jp) and open BLAST (Basic Local Alignment Search Tool) . We can then take a small segment of DNA or protein
sequence we have isolated and compare that to every one of the billions of known sequences lodged in databases worldwide. The results are available within minutes! Analysis of homology with other proteins
will then help us identify our protein. If we then go to the Expasy Proteomics Server (http://us.expasy.org/), simply by typing the name of the protein of interest we can access the TrEBML data set for the protein
in which you can find links to the protein sequence, the nucleotide sequences with any known variants, function, subcellular
location, tissue specificity, polymorphisms, disease associations, similarities to other proteins and, for some proteins their
web site, for example www.albumin.org . Scrolling down reveals access to projected 2D PAGE analysis, 3D structures, domain structure, post-translational
modifications, the protein sequence, every known variant with references, the
ability to calculate pI and mass and access to BLAST which allows you to compare this protein to every other protein known.
Now is the stage at which to point out that it isn’t always so simple. In some
organisms, there are genes and proteins that have no significant homology to any other protein identified. For these, we can
ask questions, via web based tools as to whether the sequence is likely to be membrane bound, does it have motifs like any
other type of protein. However, there are some proteins whose properties and
functions will only be known when they are purified and assayed by traditional technology.
Nevertheless, you should go to the Expasy Server and see what is available, I
hope it will amaze you. Be warned, it is addictive and you can spend many happy hours at your computer rather than at the
So, what else is available? If you teach,
the KEGG: Kyoto Encyclopedia of Genes and Genomes available at Genome Japan gives
links to the KEGG protein network which in turn links to metabolic pathways, regulatory pathways, molecular complexes, network-network relations, network-environment
relations and diseases. The metabolic pathway pages alone are fascinating, allowing you to explore generic pathways and then
the same pathway in your organism of choice, highlighting the differences. A visit to the Human Protein Reference Database
(http://www.hprd.org/) will allow you, ultimately, to find information on every known human protein, protein localisation and
tissue specific expression. A simple click will then take you to all the known information on that protein. This site is still
collating information, but, even now it is an impressive resource. Protein microarray databases are now available at the European Bioinformatics Institute
http://www.ebi.ac.uk/Databases/microarray.html and here you can visualise some of the many available microarray datasets. There are also pages with
links to all the important databases, for example http://www.biol.rug.nl/mbp/ListDatabases.htm#PD. The internet also has allows access to on-line tutorials that will help you realise the potential of
proteomics (see footnote)
Proteomics and bioinformatics are being used extensively by pharmaceutical companies interested in drug targets and modelling potential protein-drug interaction. Microarray technology
is proving to be a fast primary screen for drugs and ligands. In vaccinology, potential targets are being found using a combination
of traditional biochemistry and proteomics. Modelling studies are allowing refinements
of drugs and ligands to improve binding characteristics. Protein microarrays
are also finding a place in the analysis of antibodies in a variety of context, for example in the understanding of antibody-antigen
binding, analysis of antibody variants to determine and improve specificity and
in auto-immune disease for the identification of antigen targets.
In microbiology, comparative
genome analysis (http://www.webact.org/) allows us to visualise potential areas associated with
pathogenicity by comparing pathogenic and non-pathogenic strains.
In the hunt for surrogate disease
markers of cancer, a range of traditional biochemical techniques, such as chromatography and 2D PAGE can allow us to determine whether the production of individual proteins are up or down regulated, whether some proteins are not expressed post mutation
or whether there are novel proteins associated
Will proteomics replace “wet
“ science. The answer must be no, as the databases are reliant on information produced by the traditional “wet”
approach. There are also drawbacks to predicting structure, pI and mass as if
your protein is heavily glycosylated for example, the real values will not reflect those obtained for the simple polypeptide
chain. However, proteomics will enhance “wet” science, providing rapid assessments, screening and novel technologies.
In my opinion, now is the time to start exploring!
If you would like to run through
tutorials, access references or attend courses or meetings on proteomics, information can be obtained by going to our proteomics
tutorial website. http://www.mydocsonline.com/pub/greenwp/proteomics