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In principle, protein
folding can be understood through interatomic
interactions. If you analyze the potential
energy of a molecule as a function of the structure of
the protein, the conformations which are most often
observed are those which have the lowest energies. The
protein packs itself in a manner which maximizes
favorable interactions and minimizes unfavorable
interactions, just as a collection of small magnets will
tend to link up with north and south poles aligned.
Computer simulation methods are able to mimic this
process (albeit with a number of simplifying assumptions)
resulting in simplified models of the packing process
such as illustrated below.
Energy minimization of a peptide structure.
Proteins, then, are
chains of molecules able to wrap around themselves under
the influence of the forces between their constituent
atoms and between their atoms and water. The resulting
shapes control the function of the protein and we examine
this facet of protein science in the following section.
However, given the importance of the precise sequence of
atoms within a protein how can nature set about perfectly
reproducing copies of protein molecules to satisfy the
demands of a complex organism? The answer to this
question shows us again the importance of chemical
interactions, again in the form of hydrogen bonds, and
nature's ability to exploit such chemical forces to copy
and transfer information.
Whenever you use a
computer (or use any one of the electronic appliances or
microchip-controlled devices which now permeate the
world) you have used a stored sequence of instructions.
The instructions, like the directions that accompany that
electronic appliance, explain how to achieve a given
effect. They enable a device such as a computer to be used a
in variety of different ways - to process words or to sum
numbers in a spreadsheet - and turn a useless but fast
collection of electronic switches into a business tool or
an enthralling game. The term code is often applied to
the stored sequence of instructions that enable the
computer to respond to its external stimuli supplied by
the keyboard, mouse or pen. In manufacturing the use of a
stored sequence of instructions significantly predates
their electronic applications. In fact in 1800 Jacquard
used a sequence of instructions stored on punched cards
(a medium later exploited by the programmers of
computers) to control the production of intricate
patterns by automated looms and insuring reproducibility
and fashionability for French weavers.
A code is a source of
information which, after appropriate processing, may be
acted upon. Nature requires a code which may be used to
maintain the plans for protein sequences
(once formed in the appropriate environment) the protein
itself will adopt the required overall shape -
storing the required three dimensional information within
itself. But the sequence information must come from
somewhere. Not only must this be stored, but also ideally
there must be a mechanism permitting the transfer of the
information to succeeding generations of cells and
organisms.
Although life on earth
is so outwardly diverse a tremendous linkage between life
forms is evident in the code carrier which was discovered
at the culmination of a chain of scientific discoveries
by James Watson and Francis Crick in 1953. Their simple
model provided an explanation of not only molecular
replication, exploited by all life on earth, but also the
chemical interactions which underlie reproduction and
genetic inheritance. The model that emerged had the power
to rationalize diverse lines of existing evidence and the
truth to provide the basis for remarkable predictions and
new fields of research. The discovery of the double helix
by James Watson and Francis Crick and their colleagues
Maurice Wilkins and Rosalind Franklin is one of the most
successful models ever proposed.
The molecule that
conveys all genetic information is illustrated in the rotating
image above. The feature discovered by James Watson
in building cardboard models, which makes these molecules
so special is the fact that by a subtle pattern of bonds,
the same hydrogen bonds which are seen in protein, ice
and water, these molecules pair in a very distinctive
way. This complementary pairing of bases, shown in the
image to the left, means that, under appropriate
conditions, a chain of these base molecules can pick up a
chain of matching bases to form a complementary strand.
Watson and Crick realized that this must be the case and
showed how a helical arrangement of two associated
strands of nucleic acids could explain the diffraction
evidence gathered by the crystallographers, Maurice
Wilkins and Rosalind Franklin. The now famous double
helix, illustrated above, had been discovered.
Watson and Crick's
discovery of the registry of two chain molecules,
entwined in DNA's helix, snapped many important
observations into place. Biologists had reasoned out the
molecular size of the genetic information-carrying
component of the cell, chemists had determined the logic
of its elemental combinations. In 1953 the two scientific
fields became entwined.
The DNA molecule
conveys critical information and that makes it centrally
important. The double helix, held together by hydrogen
bonds, uses its component bases to code for the sequence
of amino acids in proteins. Thus for example adenine,
adenine, adenine in the base sequence of a DNA molecule
is translated into a particular component of a protein
molecule. Now proteins are the multi-talented catalysts
and molecular work horses, carrying vital oxygen and
providing the mechanical power of muscles for example,
and like DNA itself, proteins are long chains of
component molecules. Nucleic acids carry in their
sequence of bases the codes necessary to build the vast
range of different protein molecules that are needed by
complex organisms. The sequence of steps that form the
basis of this extraordinary storage and use of
information are now quite well understood. Transcription
is a molecular level process involving careful reading of
the DNA sequence, collection of the appropriate
constituents and their concatenation to produce a protein
molecule. The DNA molecule contains not only the
information to build protein molecules but also contains
a templated copy of itself and this is the key to
molecular reproduction, cell division and life. A simple
computer generated image conveys the essence of the
secret of DNA. A single double helix of DNA is uncoiled
and each strand of the double helix is complemented with
appropriate bases to form two helices where one had been.
The helical information carrier is then perfectly copied.
This the basis by which cells are able to divide and
organisms grow. By pairing strands of DNA from different
cells modified child helices are produced which combine
the characteristics of the parent DNA molecules. This is
the basis of inheritance. The secret of life is contained
in the helix of DNA. Scientists have gradually learned
more of the intricate mechanisms by which DNA is
controlled within the cells of living organisms. The
picture which has emerged is complex and intricate and
built around the beautiful simplicity of the helical
information carrier, DNA.
Is it possible that only as the single dominant means of
propagating molecular information could have emerged from
the turbulent chemical activity billions of years ago?
There is at present a single known exception to revive
one's faith in the diversity of propagation mechanisms
explored by life. This exception comes in the form of a
'prion', a protein, which reproduces by commandeering the
reproductive machinery of the cells of other species. The
disease 'scrapie' in sheep is caused by the hijacking of
the sheep's cells by a prion. It is not known how this
parasitic protein is able to make the host cell produce
prion molecules, but it is known that the infection is
transmitted without the involvement of DNA and that
prions themselves contain no nucleic acids and yet are
able to infect and thereby reproduce.
A schematic illustration
of DNA replication. Division of the original pair of base
strands, shown in blue, leads to two identical copies of
the base sequence.
As far as is known
then, prions are an isolated instance of molecular
opportunistic marauder. Nucleic acids and the information
they convey underlie all other forms of life. This
molecular information has enjoyed considerable success.
Why should that be? DNA efficiently conveys information,
with remarkable fidelity, so that efficient molecular
machines or proteins pass to successive generations. But
DNA also allows for the combining of information from two
individuals, through the combining of two strands of DNA
to make a single child molecule, which combines the
genetic information of the parent molecules. This pairing
of information sources allows the molecules of life to
successfully contend with changing environments and
situations. Not all life forms need to exploit this
capability, but for many it turns out to be advantageous.
Successive generations are not identical parental copies
with the parent's strengths and weaknesses
reproduced, instead they are unique individuals built
from elements of the genetic codes of both parents. When
you see a baby who has clearly inherited her
mother's eyes, you are looking at a large tract of
copied genetic code with instructions for the manufacture
of pigment and proteins. All things being equal, the
father's code will be evident in other areas of the
child's makeup.
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