Proteins Made To Order 51
ananyo writes "Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task. Now researchers report that they can do just that. By following a set of rules described in a paper published in Nature (abstract), a husband and wife team from David Baker's laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. The work could eventually allow scientists to custom design proteins with specific functions."
hello -- (Score:5, Informative)
This is actually a fairly important discovery. The poster of the article seems to be completely clueless as to why it is important.
Without going into all of the details, being able to predict the shape of proteins is one of the things needed to make nanotechnology fulfill its potential - to build a nanotech "assembler".
If you want all the details you would have to go back to "Engines of Creation" by Eric Drexler.
Proteins of the right shape can be used to create complex structures - anything from a virus to a nano-computer. Construct some RNA, feed it into a cell and get back as many copies of the protein chain as you please.
Do this for several different proteins.
Leave all of these proteins in the same chemical soup and they will combine on their own to form the more complex structuresl
But if you can't predict the shape the protein folds into, you can't get started. This has been a key problem in nano-tech going back to the 1970s.
David Baker, you wonderful man (Score:3, Informative)
I used to work in a protein engineering lab that collaborated extensively with Baker's lab. Let me be the first to say the quality of work coming out of there is outstanding. Protein engineering is incredibly difficult and their Rosetta software (protein folding again) is pretty much essential (yeah yeah, there's other software and rosetta has flaws, like not taking charged amino acids into account, but really its the best we have) -- even more so than pymol for any design you'd be doing.
This is the second large break through coming from them in the past few years. The other one was designing enzyme that performed a totally novel reaction. Details here: http://www.sciencemag.org/content/329/5989/309 . I really can't stress how big of a deal this is for designed (chemical) molecules. Even if the reaction wouldn't have happened under normal conditions or without causing decomposition to the rest of the molecule, you can make an enzyme that will do it for you.
This study should help the creation process, generally directed design runs into a lot of problems with proteins that no longer fold. Being able to determine computationally what has a chance of working would greatly speed up the process. Beyond that congrats to the lab and one of the most hands on, in the science PIs I know
Re:This is really important (Score:2, Informative)
I don't think OP did a great job of explaining kinetic perfection, so I'll try to expand on it.
Firstly, I've generally heard it referred to as catalytic perfection, not kinetic. Regardless, it means that
1) every enzyme-substrate collision is productive, that is, generates a product and
2) the reaction happens in less time than the enzyme and substrate can find each other in solution.
This means that the "limiting reagent" of the reaction is the diffusion speed of the enzyme and substrate - if enzyme and substrate(s) could encounter each other in less time, they would (might) react faster. Some enzymes can surpass this limit by having an arrangement of charged amino acid residues on the surface that creates an electric field about the active site which accelerates the substrate toward the enzyme, causing it to move faster than the diffusion limit. It also serves to orient the substrate properly (ie, negatively charged portion of substrate moves toward positive portion of the enzyme, etc), ensuring that the substrate lines up properly in the active site for optimal catalysis.
I wouldn't say that "how they manage their astounding speed is one of biology's great unsolved problems," because such a statement is an extreme oversimplification of the problem. Many enzymes use catalytic mechanisms that are completely different from each other, and as a result, there isn't a general solution to explaining the rate enhancements that they afford. There are many factors that enzymes combine to enhance reaction rates though, such as stabilizing the transition state, correctly orienting substrates, and so forth. Some of these are well understood conceptually, but how they play a role in specific proteins is not. However, many catalytic mechansims are reused, so figuring out how one enzyme works may help to elucidate the mechanism of similar enzymes. But it also may not. For example, class I and class II aldolases have entirely different mechanisms (one has metals in the active site, the other does not).
Regardless, I agree with your assessment of the importance of the enzymes as molecular factories. I am very excited to see what the future holds.