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Designing Proteins In Silico
Fluorophore writes "In a recent issue of the scientific journal Nature, scientists in the lab of Homme Hellinga at Duke University reported designing proteins using a cluster of 20 computers. These proteins were then tested in the lab and shown to bind their intended targets including TNT, serotonin and lactate. This is a tremendous step for computational biology, nicely reviewed in C&E News' top story. Designer proteins such as this can be developed for bioremediation of weapons dump sites (TNT) and sensitive sensors of drugs/contaminants that can easily be grown in bacteria."
One of the mantra of proteomics is that structure equals function. So increasing protien function increases the exactness of what structure must be.
Creating a self replicating protien would require insertion of a encoding sequence of dna of the host. And the self replication would involve that protien doing something like functioning as a promoter for that sequence, thus requiring a portion of the structure of the protien be able to recognize a specific sequence of DNA.
Creating a malicous or beneficial protien indicates that it has a specific target (such as a specific receptor on the HIV protien coat). This also requires a specific structure to be able to recognize that.
The problem with computationally designing a protien that both self replicates and serves a malicious or beneficial purpose is that the computation involved increases exponentially when adding a new function to a protien.
This is because you may get a structure that works well for one of the two targets, but then you have to check it against the other target, and it may work horribly for that second one. So then you repeat the cycle until you find something that works well for both.
So while it is technically correct that they could do it, it's going to be a difficult thing to do by computational methods (and probably even harder by conventional methods).
The actual Nature article is "Computational design of receptor and sensor proteins with novel functions," in the May 23, 2003 issue (Vol 423 No 6936 pp101-205). It is important to note that they are not making fully functional enzymes yet, but have accomplished the rather daunting task of designing/directing the evolution of a given protein binding substrate A and making it bind a new, completely different substrate B. Their wild-type substrate interacts with 12-18 residues, so multiply that by your 20 standard amino acids across these interacting residues and you have a crapload of sequences to deal with (10^15 to 10^23; I'll take their word for it). I thought the statement "Designer proteins such as this can be developed for bioremediation of weapons dump sites (TNT) and sensitive sensors of drugs/contaminants that can easily be grown in bacteria." was kind of cute as when you search Pubmed with "TNT reductase" you get back a number of articles on bacterial enzymes that allow them to munch TNT. A few years back I got to work on a project to solve the structures of enzymes that pop NO2 groups off of TNT and related compounds; the bacteria that these proteins were subcloned out of were found in the heavily contaminated soil of a former World War 2 munitions plant. Pretty cool what evolution can do when you add a new component to the environment of some organism.
These proteins were then tested in the lab and shown to bind their intended targets including TNT, serotonin and lactate.
Exactly what we need to target those pregnant depressed suicide bombers!
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