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."

Comments

Creating artificial drugs

[Khyber]

Well, we know we've been able to modify DNA to produce insulin from bacteria.

We've got bacteria that crap out metal wires (Can't remember if we discovered them or made them)

Now where's the bacteria that will make substances like xanax or other drugs, so it can make the entire market cheaper and more affordable to those who need it but don't have insurance, and "naturally" at that? (Naturally as in not needing a buttload of power from a processing plant for the drug and wasting energy uselessly)

Re:Creating artificial drugs

[k98sven]

Now where's the bacteria that will make substances like xanax or other drugs, so it can make the entire market cheaper and more affordable to those who need it but don't have insurance, and "naturally" at that? (Naturally as in not needing a buttload of power from a processing plant for the drug and wasting energy uselessly)

Um.. news flash: Drugs have been made that way for years.

But first: This works for proteins such as insulin. Most drugs are not proteins, however.

And for those who are, there is nothing about it which necessarily makes it cheaper or less power-consuming. Bacteria need food. Bacteria need to be kept warm. And most importantly, you've got to seperate and purify your drug from the bacteria and growth substrate and whatnot.

Of course, for proteins you've got no choice. It's practically impossible to synthesize proteins using conventional chemistry. And it's very very difficult (and likely uneconomical) to use bacteria to produce other organic compounds. So these things are complimentary to eachother, really.

Re:I hate to turn this into a flamewar so soon, bu

[salemnic]

I think you might be using backwards logic here. TFA states that by examinig 100 proteins they were able to notice some standard common things about the proteins they were looking at. When they made rules around those common things they could make new proteins.

It's like having 100 pieces of example code to look at before trying to create your own, not generating the code from nothing.

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Link to Nature article

[JuliusSu]

Full text of article, institutional/personal subscription required.

Abstract: Classical studies show that for many proteins, the information required for specifying the tertiary structure is contained in the amino acid sequence. Here, we attempt to define the sequence rules for specifying a protein fold by computationally creating artificial protein sequences using only statistical information encoded in a multiple sequence alignment and no tertiary structure information. Experimental testing of libraries of artificial WW domain sequences shows that a simple statistical energy function capturing coevolution between amino acid residues is necessary and sufficient to specify sequences that fold into native structures. The artificial proteins show thermodynamic stabilities similar to natural WW domains, and structure determination of one artificial protein shows excellent agreement with the WW fold at atomic resolution. The relative simplicity of the information used for creating sequences suggests a marked reduction to the potential complexity of the protein-folding problem.

From this page : a WW domain is the smallest, monomeric, triple-stranded, anti-parallel beta-sheet protein domain that is stable in the absence of disulfide bonds, cofactors or ligands.

Re:Name that film...

[ScrewMaster]

Nope. From the original movie "The Fly" with David Hedison.

For the benefit of the slashdot crowd

[soren.harward]

Since protein engineering is my field of study, for the benefit of the /. crowd (and my karma) I'll fill in the gaping holes left in the New Scientist article, and give you a little more background on the Nature paper. Because the writeup on /. is a perfect example of "scientific telephone": a semi-interesting result gets written up into a paper, which once it's been through several layers of editors suddenly seems like a major breakthrough.

The Nature paper isn't a breakthrough. It's not even really a major advance. Scientists in my field have been creating artificial proteins for five to ten years now. And yes, even some of them designed completely from scratch (though they're really simple; nothing as complex as, say, ATP synthase) instead of just taking a known fold pattern, known as a "motif." The "WW domain" (domain, in protein parlance, is a small, independent structure within a much larger protein---think of it like a module within the kernel or Apache) is a common fold in hundreds of different proteins. Basically, they analyzed the sequences of all of these WW domains, and figured out which positions were meaningful. It's kinda like reading through some code in a programming language you don't know, and figuring out which lines are comments and which lines are actual compilable code. This group found that the number of interesting positions is small, that they could identify them just from the amino acide sequence instead of having to mess with the whole complicated 3D structure of the domain, and that if they put together a protein with the meaningful amino acids intact and the non-meaningful positions randomized, then in many cases they could still get a pretty decent protein (in terms of structural similarity to the "natural" protein) out of it. Most of the paper is devoted to showing via various methods that they did get a pretty decent protein.

So what does this mean for me, assuming that this paper is absolutely correct (which I admit is a little hard for me to determine with one quick reading, given that I'm just a first-year grad student)? It means that the number of meaningful amino acids in a protein (at least in terms of overall structure) is pretty low, and that they can be identified without knowing what the full 3D structure is. This is good, because for a lot of proteins, the 3D structure is difficult to get. However, they picked an easy target: a small domain where there are over 100 unique sequences known. We'll see how well this method holds up with longer domains and fewer unique sequences. The S/N ratio won't be nearly as good.