Deciphering The Message of Life's Assembly

[Excerpt] In nature, there's a huge assortment of attractive and repulsive forces that atoms can exert on one another. But Rose and Srinivasan theorized that protein folding, no matter how it worked, had to be pretty simple. So they stripped the chemical rules of their program down to the bare minimum.

First, they specified that no two amino acids could occupy the same space at the same time. Second, they said that oil-loving amino acids would tend to bury themselves inside the folded protein, while water-loving amino acids would tend to be on the protein's surface, which is usually surrounded by water. The third rule was that the amino acids would be permitted to interact with one another through "hydrogen bonds," which are weak chemical attractions that, multiplied many-fold, help linear molecules twist or lie in a regular way.

With the one principle and the three rules, the researchers tried out their computer simulation.

To simplify things, they used 50-amino acid pieces of known proteins, instead of whole proteins. They fed the amino acid sequence -- Position No. 1 through Position No. 50 -- into LINUS, their computer program, and asked it to fold up the chain. They then compared the result to the actual structure, which was known from X-ray crystal analysis.

The simulation works like this:

LINUS rotates three consecutive amino acid beads in the chain by a random amount. This kinks the entire chain, sometimes a lot and sometimes a little. The computer then evaluates each amino acid's relationship to those near it -- specifically to the six on its left and the six on its right. Most of the time, these randomly generated shapes are physically impossible, and the computer moves on, rotating the next three beads. When an "allowable" shape arises, however, the program calculates its energy.

The computer keeps the chain in its previous shape unless the new shape it creates has a lower energy. When that happens, the new shape is adopted and the old one is rejected. This random trying out of poses goes on until the last three beads are rotated. The pose -- or conformation -- that remains at the end of a run is then stored in LINUS's memory.

LINUS walks up and down the amino acid chain 6,000 times, creating 6,000 final poses. This is only a fraction of the possible conformations a chain of amino acids can take, but statistically it's a big enough sample to explore the "territory" of possibilities. LINUS then sits back and takes a look.

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Read the entire paper here.





This article is from Protein Design
http://www.proteindesign.com/