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Creating Artificial Proteins
Spy der Mann writes "By examining how proteins have evolved, UT Southwestern Medical Center researchers have been able to design genes to create artificial proteins.
The researchers have discovered a set of simple "rules" that nature appears to use to design proteins. By feeding these rules into a computer program, they were able to obtain a sequence of artificial genes. These genes were then inserted into laboratory bacteria, producing the artificial proteins as expected."
This seems like a very, very simple way of tagging people. I.E., if you can make a protein that can't occur in the body naturally, inject it into someone when you do something to them. Kind of like having the P on the wrists of pirates, except it avoids all those "social stigmatization" arguments... but allows foreign governments (or whoever) to see that they've been marked. Interesting....
And the answer to this could be that a lot of rules have been randomly tried out. It turns out that the rule(s) we are seeing/discovering are the ones that lasted - and if they are simple they are probably efficient in some way.
The creationist/ID policy is to avoid facing unknowns by passing the buck onto a designer. In the current example, just because something appears elegant and simple to some person, it does'nt mean that it could not have naturally occured.
Our jobs, as scientists, or in the more general case, as people with a scientific temperement, is to uncover how or why this simple and elegant thing is the way it is - not to say, 'It's too tough, lets pass the buck onto the designer'!
Artificial proteins! YES! One step closer to Artificial steak!
Can this be used for information compression in any way? After all, it was discovered about 20 years ago that simple fractal equations gave shapes very much like ferns. This could give you a shorthand way of compressing the genome of an organism, then making comparisons.
It would also, of course, be interesting if you could use this to work backwards through the genome to a set point, and (hypothetically) bring back the Auroch.
Personally, I want to see how this deals with metal incorporation at the active site, and whether their selection rules work for that as well.
the more accurate the calculations became, the more the concepts tended to vanish into thin air. R. S. Mulliken
Why can't these articles include any meaningful information? They refuse to tell you what they're about.
Earlier research has shown that for a given group of related proteins, or protein family, all family members share common structures and functions.
What would be an example of a "protein family" in this context? Filamentous? Membrane associated? Globins? Antibodies? No idea. "Common structures and functions" could mean several different things.
By examining more than 100 members of one protein family, the UT Southwestern group found that the proteins share a specific pattern of amino acid selection rules that are unique to that family.
This tells us nothing that isn't already known. Of COURSE proteins with related functions share specific patterns of amino acid selection rules or they wouldn't work. WHAT sort of selection rule did this group actually find?
"What we have found is the body of information that is fundamentally ancient within each protein family, and that information is enough to specify the structure of modern-day proteins," Dr. Ranganathan said.
He sounds like he's talking to a little kid.
He and his team tested their newly discovered "rules" gleaned from the evolutionary record by feeding them into a computer program they developed. The program generated sequences of amino acids,
and how did it do this?
which the researchers then "back-translated" to create artificial genes.
i.e. they did a trivial replacement of single amino acid letters with three letter codons in silico, then generated the corresponding DNA sequence.
Once inserted into laboratory bacteria, the genes produced artificial proteins as predicted. "We found that when isolated, our artificial proteins exhibit the same range of structure and function that is exhibited by the starting set of natural proteins," Dr. Ranganathan said. "The real test will be to put them back into a living organism such as yeast or fruit flies and see how they compete with natural proteins in an evolutionary sense."
Translation from stupid-articlese: in vitro the translation products of the artificial DNA folded into shapes similar to wild type proteins. I think.
One can only assume that these guys chose proteins that don't undergo post-translational modification.
If that was all they'd done I find it difficult to see how this differs from doing a multiple sequence alignment for a family of proteins, then making a gene for the consensus sequence.
Checking the paper (and related News and Views article) in Nature itself (http://www.nature.com/nature/journal/v437/n7058/i ndex.html ) (subscription required) indicates they've done more than that. By including the effects of coevolution - where one position in the protein mutates in concert with another to maintain optimal contacts - they generate a substantially better algorithm for manufacturing particular folds. (ie: 25% success in achieving folding versus 0% for conservation alone. 60% presence of wild-type function in the 'designed' proteins.)
Interesting, but I'm suprised it made it into Nature. (OK then, jealous...)While I realize this news seems fascinating to some individuals, it is not something so entirely new that people in Computational Biology would consider it groundbreaking. Using the computer algorithms to generate new gene sequences is actually just a matter of running the gene finding algorithms you used to find these genes backwards (in fact, many people have been testing their gene finding algorithms by using their old algorithms to generate pseudo test sets). The only thing new about this paper is that people actually went forward and experimentally validated their results. An interesting find, however, the end result does not provide a huge leap to science.
Now, if people are really interesting in some neat ways of reengineering genes back onto themselves, then they should take a look at some of the work being done with synthetic circuits. The beauty of synthetic circuits is that since you already know how the genes will function, it's just a matter of setting the circuit up in the fashion that you want so that it produces the end result that you want. There really is no limit to what you can do with synthetic circuits (of course, researchers have a long way to go before they master and understand all the regulatory mechanisms). For example (and these are all very theoretical examples): building a cell circuit to release a drug into a body in a very time released fashion (and perhaps autonomously renewing, for example, building a circuit to release insulin into the body given the sugar level of the individual), designing a circuit to recognize and destroy tumors (or perhaps an even simpler form of designing a circuit to recognize and fluorescently label tumor cells in the body helping in removal/early detection). Of course, one could also build quite malicious synthetic circuits as well. For example, a circuit that would aggregate to the wall of the heart and, after a certain number of other cells accumulate, triggering a signal to all the malicious cells and destroy the heart in unison.
The other nice advantage of synthetic circuits is that the more we learn out regulatory mechanisms in species, the more we can use them for synthetic circuits. The more we use them for synthetic circuits, the more we understand about how exactly the underlying mechanism works (what causes them to break, how do they deal with differing toxic environments, etc). It creates a nice feedback loop with the progression of science.
There will come a day where it will be useful to generate new DNA/Proteins in combination with synthetic circuits, but, as noted in a previous post, we don't understand the relationship between protein sequence and structure/function enough for it to be a viable option (and this is just with how the protein folds, we haven't even gotten in to the problem of gene regulatory structures-- multiple gene splicing, chromosome structure elements, binding motifs, translational regulation, etc). In fact, this area is something we probably want to venture into as it provides us with an even finer control over the rate constants for synthetic circuits. But for now, the generation of randomly generated genes based on prior genes will go overlooked for quite some time.
I do not pretend to be an expert, or actually know anything about the subject and to promote Slashdot standards on information digesting, didn't actually read the article. But if one creates proteins that are exactly as nature would manufacture the real thing, why are they called artificial? They are the real thing!
PDFs of our papers, and Java code implementing 4 different correlated mutation algorithms including SCA, are at my web site:
http://www.afodor.net
The references are:
Anthony A. Fodor, Richard W. Aldrich. On Evolutionary Conservation of Thermodynamic Coupling in Proteins. JBC 279(18):19046-19050, 2004
John P. Dekker, Anthony Fodor, Richard Aldrich and Gary Yellen. A pertubation-based method for calculating explicit likelihood of evolutionary co-variance in multiple sequence alignments. Bioinformatics 20:1565-1572, 2004
Anthony A. Fodor and Richard W. Aldrich. Influence of Conservation on Calculations of Amino Acid Covariance in Multiple Sequence Alignments. Proteins 56(2): 211-221, 2004
The last paper contains a comparison between SCA and three other correlated mutation algorithms.
As I said, I haven't had a chance to look carefully or critically at the new papers. (It takes me a LONG time to read a paper critically :-> This Slashdot thread will be likely long archived before I finish thinking about these papers!). But this particular algorithm aside, people who are interested in bioinformatics and contact prediction may find the math behind the correlated mutation algorithms interesting.
Anthony
Email: anthony.fodor(remove this and put in an at symbol)gmail.com
http://www.afodor.net/
a whole new host of PRIONS for us to endure.
Why are there symbiant relationships? It allows for division of labor, essentially. The genetic load of one organism after symbiosis does not have to take care of these certain task that the other is taking care of. Most of the cells contained in your body are not actually yours. The majority of cells in the body are bacteria living in your intestine which each produce proteins which help with digestion. If our DNA had to encode for every one of those digestive and metabolic proteins that are actually used in digestion, we would be selected against compared to an organism that could make more efficient use of its DNA.
Diversity also leads to a sort of long term stability. If there are different ways to obtain resources, the ecosystem as a whole can adapt to environmental changes far more gracefully.
I'll never make that mistake again, reading the experts' opinions. - Feynman
Yeah, exactly. Natural selection is pass/fail, there are no As, Bs, etc. :-)
Furry cows moo and decompress.
"This tells us nothing that isn't already known. Of COURSE proteins with related functions share specific patterns of amino acid selection rules or they wouldn't work""
This cannot be assumed; while logical on the surface, that's like saying that porpoises and sharks must be from the same family because they both swim in the ocean and have the same body shape. The scientific method DEMANDS that a hypothesis like that is tested.
"He sounds like he's talking to a little kid. "
In terms of protein chemistry, he probably is talking to to little kids. This article is basically a publicity press release, and is not intended for the scientific community -- their papers in Nature are intended for the scientific community.
and how did it do this?
While you're at it, why don't you ask that any articles about scientific research include the entirety of the published paper(s)? What is important to the casual reader (which is the intended audience) is not the how, but the what and the why.
"One can only assume that these guys chose proteins that don't undergo post-translational modification."
No, one can't assume that. One must read their published papers before leaping to conclusions. Think a bit: if the DNA was expressed in the bacteria, could the proteins not undergo the same post-translational modification as naturally occurring proteins? The research conducted did not test to see what happened during expression, it just tested the form and functionality of the end result, as far as I can tell FTA.
You shouldn't get all worked up because an article intended for the general public isn't detailed enough for you. Many people wouldn't even bother to read TFA (even if they could understand it) if it was written in anything other than plain english.
Someone like you, who wants better information (which is a good thing) should go down to the library at the end of the month and read the published papers in Nature.
"Trolls they were, but filled with the evil will of their master: a fell race..." -- J.R.R. Tolkien on Olog-hai
I've been on enbrel for six months now to treat my psoriasis (think lizard man from lepar island, not just crusty elbows). It's a protein that I have to inject twice a week since taking it orally would end with my body digesting the meds. I could see genetically engineering a bacteria that could live in the intestine and produce the medicine. That would be awesome.
Disconnect your television. Do your own research. Draw your own conclusions. They're probably lying. Don't be a sheep.