| Topic: |
Science > Philosophy |
| User: |
"Sir Frederick" |
| Date: |
25 Sep 2006 08:36:44 AM |
| Object: |
Protein folding (prion) home computer assistance |
This is a distributed computing project to study prions (protein
misfolding), that results in diseases such as Mad Cow, and is believed to
cause Alzheimers and others.
You can download one of the projects programs to make your home computer
part of a supercomputer to study prions. The URL is here:
http://folding.stanford.edu/
This looks like a very good thing to volunteer for.
Martin
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| User: "Immortalist" |
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| Title: Re: Protein folding (prion) home computer assistance |
25 Sep 2006 11:48:29 AM |
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Sir Frederick wrote:
This is a distributed computing project to study prions (protein
misfolding), that results in diseases such as Mad Cow, and is believed to
cause Alzheimers and others.
You can download one of the projects programs to make your home computer
part of a supercomputer to study prions. The URL is here:
http://folding.stanford.edu/
This looks like a very good thing to volunteer for.
Martin
The process of protein folding, while
critical and fundamental to virtually all
of biology, in many ways remains
a mystery.
Its not really a mystery what is causing the folding but the mystery
comes in when trying to determine which of various factors are
contributing to a fold at any particular time. Its as if the genes
direct the assembly of jigsaw puzzle peices and their particular
connectability to other peices in the puzzle by edge definition. More
like these proteins are the real "bricks" in the assembly itself. Even
though there are other influences besides the genes it could be as if
the genes combine the down-hill road to organizarion to its advantage,
it "steers" these othere forces but they won't tell you that now will
they.
----------------------------------
wikigoogleyahoohoo
Proteins are large organic compounds made of amino acids arranged in a
linear chain and joined by peptide bonds. The sequence of amino acids
in a protein are specified by a gene and encoded in the genetic code.
Although this genetic code specifies 20 "standard" amino acids, the
residues in a protein are often chemically altered in
post-transcriptional modification: either before the protein can
function in the cell, or as part of control mechanisms. Proteins can
also work together to achieve a particular function, and they often
associate to form stable complexs.
Like other biological macromolecules such as polysaccharides, lipids,
and nucleic acids, proteins are essential parts of all living organisms
and participate in every process within cells. Many proteins are
enzymes that catalyze biochemical reactions, and are vital to
metabolism. Other proteins have structural or mechanical functions,
such as the proteins in the cytoskeleton, which forms a system of
scaffolding that maintains cell shape. Proteins are also important in
cell signaling, immune responses, cell adhesion, and the cell cycle.
Protein is also a necessary component in our diet, since animals cannot
synthesise all the amino acids and must obtain essential amino acids
from food. Through the process of digestion, animals break down
ingested protein into free amino acids that can be used for protein
synthesis...
....Proteins are the chief actors within the cell, said to be carrying
out the duties specified by the information encoded in genes. With the
exception of certain types of RNA, most other biological molecules are
relatively inert elements upon which proteins act...
Most proteins fold into unique 3-dimensional structures. The shape into
which a protein naturally folds is known as its native state. Although
many proteins can fold [(unassisted)] simply through the structural
propensities of their component amino acids, others require the aid of
molecular [(chaperones)] to efficiently fold to their native states.
Biochemists often refer to four distinct aspects of a protein's
structure:
Primary structure,
Secondary structure,
Tertiary structure,
Quaternary structure
- (see below) -
....The most successful type of structure prediction, known as homology
modeling, relies on the existence of a "template" structure with
sequence similarity to the protein being modeled; structural genomics'
goal is to provide sufficient representation in solved structures to
model most of those that remain. Although producing accurate models
remains a challenge when only distantly related template structures are
available, it has been suggested that sequence alignment is the
bottleneck in this process, as quite accurate models can be produced if
a "perfect" sequence alignment is known. Many structure prediction
methods have served to inform the emerging field of protein
engineering, in which novel protein folds have already been designed. A
more complex computational problem is the prediction of intermolecular
interactions, such as in molecular docking and protein-protein
interaction prediction.
The processes of protein folding and binding can be simulated using
techniques derived from molecular dynamics, which increasingly take
advantage of distributed computing as in the Folding@Home project. The
folding of small alpha-helical protein domains such as the villin
headpiece and the HIV accessory protein have been successfully
simulated in silico, and hybrid methods that combine standard molecular
dynamics with quantum mechanics calculations have allowed exploration
of the electronic states of rhodopsins...
....Primary structure: the amino acid sequence
Secondary structure: regularly repeating local structures stabilized by
hydrogen bonds. The most common examples are the alpha helix and beta
sheet. Because secondary structures are local, many regions of
different secondary structure can be present in the same protein
molecule.
Tertiary structure: the overall shape of a single protein molecule; the
spatial relationship of the secondary structures to one another.
Tertiary structure is generally stabilized by nonlocal interactions,
most commonly the formation of a hydrophobic core, but also through
salt bridges, hydrogen bonds, disulfide bonds, and even
post-translational modifications. The term "tertiary structure" is
often used as synonymous with the term fold.
Quaternary structure: the shape or structure that results from the
interaction of more than one protein molecule, usually called protein
subunits in this context, which function as part of the larger assembly
or protein complex.
In addition to these levels of structure, proteins may shift between
several related structures in performing their biological function. In
the context of these functional rearrangements, these tertiary or
quaternary structures are usually referred to as "conformations," and
transitions between them are called conformational changes. Such
changes are often induced by the binding of a substrate molecule to an
enzyme's active site, or the physical region of the protein that
participates in chemical catalysis.
Proteins can be informally divided into three main classes, which
correlate with typical tertiary structures: globular proteins, fibrous
proteins, and membrane proteins. Almost all globular proteins are
soluble and many are enzymes. Fibrous proteins are often structural;
membrane proteins often serve as receptors or provide channels for
polar or charged molecules to pass through the cell membrane.
A special case of intramolecular hydrogen bonds within proteins, poorly
shielded from water attack and hence promoting their own dehydration,
are called dehydrons.
http://en.wikipedia.org/wiki/Protein
Protein engineering is the application of science, mathematics, and
economics to the process of developing useful or valuable proteins. It
is a young discipline, with much research currently taking place into
the understanding of protein folding and protein recognition for
protein design principles.
There are two general strategies for protein engineering. The first is
known as rational design, in which the scientist uses detailed
knowledge of the structure and function of the protein to make desired
changes. This has the advantage of being generally inexpensive and
easy, since site-directed mutagenesis techniques are well-developed.
However, there is a major drawback in that detailed structural
knowledge of a protein is often unavailable, and even when it is
available, it can be extremely difficult to predict the effects of
various mutations.
Computational protein design algorithms seek to identify amino acid
sequences that have low energies for target structures. While the
sequence-conformation space that needs to be searched is large, the
most challenging requirement for computational protein design is a
fast, yet accurate, energy function that can distinguish optimal
sequences from similar suboptimal ones. Using computational methods, a
protein with a novel fold has been designed[1], as well as sensors for
un-natural molecules[2].
The second strategy is known as directed evolution. This is where
random mutagenesis is applied to a protein, and a selection regime is
used to pick out variants that have the desired qualities. Further
rounds of mutation and selection are then applied. This method mimics
natural evolution and generally produces superior results to rational
design. An additional technique known as DNA shuffling mixes and
matches pieces of successful variants in order to produce better
results. This process mimics recombination that occurs naturally during
sexual reproduction. The great advantage of directed evolution
techniques is that they require no prior structural knowledge of a
protein, nor it is necessary to be able to predict what effect a given
mutation will have. Indeed, the results of directed evolution
experiments are often surprising in that desired changes are often
caused by mutations that no one would have expected. The drawback is
that they require high-throughput, which is not feasible for all
proteins. Large amounts of recombinant DNA must be mutated and the
products screened for desired qualities. The sheer number of variants
often requires expensive robotic equipment to automate the process.
Furthermore, not all desired activities can be easily screened for.
Rational design and directed evolution techniques are not mutally
exclusive; good researchers will often apply both. In the future, more
detailed knowledge of protein structure and function, as well as
advancements in high-throughput technology, will greatly expand the
capabilities of protein engineering.
http://en.wikipedia.org/wiki/Protein_engineering
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