| Oligometrics.com | "useful results" |
| Imagine you decide the complexity of biology is no
longer something to shy away from, but rather is something
you would like to embrace. Perhaps in the past, the
enormity of the problem (understanding biology) was such
that you did not know where to start, or perhaps any
starts which were attempted resulted in cul-de-sacs at
best and failures at worst. And perhaps, when considering
such things as the enormity of the universe, you realize
there is also enormity (maybe even more enormity) in a
polypeptide, when you contemplate the topic of "sequence
space." Sequence space refers to the number of possible sequences a chain can have in relation to both the length of the chain and the identity of the individual units that make up the links in the chain. If they are all the same, as in an actual chain, then the space is small. But if the units can vary, then the space grows very big very fast. The formula is u^n, where u is the number of different units one can choose from to make a chain, and n is the length of the chain. So if you want to make all the possible chains using paper loops, one red and one white, that are 5 loops long, there would be 2^5 = 32 different chains you would have to make. Since there are 20 "common" amino acids, then the pentapeptides you can make that would all be chemically distinct is 20^5 = 3.2 million. If you want to make polypeptides that verge on lengths that might be interesting with respect to taking on 3D shapes, like say, 20-mers, we have to use scientific notation: 20^20 ~ 1.04x10^26. To put this in perspective, the number of molecules in 18g of water is ~6.02x10^23 (i.e. one mole). So there are something like 174 moles of possible 20-mers! |
|
Another
way to put this in perspective, and also to connect to the
enormity of the universe, is to consider proteins instead
of peptides. Proteins can be hundreds of amino acids long.
If we stick with just a "small" protein of 100 amino
acids, then the number of possible sequences is 20^100 =
~10^130, or more than the number of particles in the
observable universe. So if you seek to do biology on a cosmic scale, then considerations of sequence space are both humbling and exciting, since there is a very real chance that in the 174 moles of possible 20-mer peptides, there is one, and probably a lot, that are interesting and will shed light on biological and chemical problems. This is really what this paper is good for, since making even a couple of 20-mers using standard solid phase synthesis is expensive and is not something you would ever do out of curiosity. But attaching a 20-mer to GFP and seeing what it does is fast and cheap. We have 300 peptides and counting! |