|
The artificial spider silk production exemplified the expertise and
skills required for successful applications in biosupramolecular
chemistry, in this case by combining genetic engineering with
sophisticated micro-manipulation techniques to optimise production of
the desired material. Firstly genes were inserted into the bacteria to
produce proteins as similar as possible to spider silk. Then
microfluidic approaches, dealing with fluids at very small scales,
were used to fabricate the silk. Finally the mechanical properties
were optimised further by substituting some of the amino acid
components of the proteins.
Other applications of biosupramolecular chemistry are further off, but
coming into range, according to the ESF workshop convenor, Professor
Anthony Davis from Bristol University in the UK. But the most
important aspect of the ESF workshop was the bringing together of
scientists in two previously distinct fields, said Davis. �Our main
aim was to get two groups of scientists talking to each other - the
supramolecular chemists, and a group of biologists who might be termed
�biomolecular engineers�,� said Davis. �Certainly this objective was
fulfilled.� Supramolecular chemists study and manipulate the
interactions between molecules in general, while biomolecular
engineers specialise in exploiting the large organic molecules found
in Nature.
Biological macromolecules include proteins comprising amino acids,
complex carbohydrates made from simpler sugar molecules, as well as
both RNA and DNA made from nucleic acids. Unlike small molecules,
these large constructions exhibit multiple chemical properties at
different parts of their surface, which means that interactions
between them depend on geometrical features. It is the geometrical
arrangement of the component parts, as much as their chemical identity,
that determines how a macromolecule will behave and interact with
other molecules both large and small. Some molecules will only react
or bind with certain others, often temporarily, on a �lock and key�
basis determined by the relative shapes of the surface. Such transient
associations between large molecules (supramolecules) are very
important in biology, for example in the binding between antibodies
and antigens in the immune response, and also between an enzyme and
its substrate, i.e. the compound it is acting upon.
These looser interactions between large molecules are called
non-covalent because they do not involve sharing of electrons, but
instead exploit variations in electrical charge distribution in their
vicinity. Since each individual bond is weak, non-covalent bonding
relies on the collective strength of multiple bonds and is therefore
only a viable mechanism for joining larger molecules together.
As well as being important for temporary binding, non-covalent bonding
forces are also essential for maintaining the structure of large
proteins, and for the DNA double helix, on a longer term basis, by
holding the components together. This is a very complex subject given
the huge number of combinations of components involved, and so a
significant advance reported at the ESF Biosupramolecular conference
by Andrei Lupas from the Max Planck Institute for Developmental
Biology in Germany was of a dictionary representing proteins by motifs,
that is smaller coherent arrangements of its constituent amino acids,
derived from studying their evolutionary history. Lupas showed how
such a dictionary could be used to derive evolutionary relationships
between proteins. This could have great application in evolutionary
biology and also for determining the role of proteins whose function
is as yet largely unknown, as well as understanding diseases where
protein interactions go wrong.
Having identified many promising avenues of research, the ESF workshop
is likely to be followed up by further meetings, according to
Davis.�We hope to organise another meeting in 2009, and maybe keep
going to create a regular series of symposia.�
|
