Another in a continuing (but disjoint) series of brief discussions about the important issues needed to understand what Rosetta is doing....

In biology, at the molecular scale (read small), a molecule's shape is the most important thing!

Why? More often than not the machinations in biological systems (the stuff that cells do, for example) is done by the interaction between things that 'fit' together.

Here's a visual aid you can do at home (bar tested): Clench your right fist. Cup your left hand and place it over your right fist so that they fit together.

OK, that's the essence of the 'lock and key' model of biological interaction - this model is used all over the place (try a Google search on 'biology lock and key' and you'll see what I mean). Your palm is a model of a 'receptor' or the lock, and your fist is a model of the key or the 'substrate'.

"For those of you from the FAD project, your palm is the 'binding site' and your fist is the 'drug'."

Now, while holding your hands locked together, note the parts of your right hand that are touching your left palm. Now, while leaving your left hand cupped in the same way, remove your right hand. Try fitting your right hand into your cupped left, aligning the parts that had been touching, without forming a fist.

You'll find it challenging to make the important bits on your right hand match up with the same places on your left hand. Go on try all sorts of orientations.

If you think about it, you'll see that only by making your hand into a fist do you bring those bits together in space so that they can align with the spots on the palm.

At this point in the bar my audience typically has moved on to other things leaving my simple little model behind...but I'll continue just a bit more.

Let's take a closer look. You'll notice that the parts for your fist that touch are on different fingers of your right hand. They aren't just adjacent, it is the act of making a fist brings spots throughout your hand together, into alignment which then provides the key that fits the lock.

This idea is very important! It is the collapse (folding) of our molecule (protein) that brings the important bits into the necessary orientation to be reactive. This is why proteins are interesting, they 'fold' in a repetitve, organized fashion to orient parts of itself so as to react with something in a specific fashion.

That's why protein folding is important. If we know the sequence of a given protein (the makeup of a protein molecule) we still don't understand how it works until we know into what shape it folds!

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This idea is very important! It is the collapse (folding) of our molecule (protein) that brings the important bits into the necessary orientation to be reactive. This is why proteins are interesting, they 'fold' in a repetitve, organized fashion to orient parts of itself so as to react with something in a specific fashion.

That's why protein folding is important. If we know the sequence of a given protein (the makeup of a protein molecule) we still don't understand how it works until we know into what shape it folds!

I just had an epiphany reading this.

I've known for some time that insulin is a hormone, and I was taught in high school biology (too many years ago now), that hormones are the body's chemical "messengers", they take a message from some part of the body to some other part.

Somewhere along the way, I found out that insulin is a fairly short protein chain. This is, incidentally, the reason it can't be administered orally. Think about it. :) This must mean that insulin does what it does by folding into its specific shape, and bonding to receptors to cause cells to start absorbing glucose, etc.

Vast oversimplifications abound in that last paragraph, but you get the general idea.

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Insulin was the Protein Data Bank (PDB) molecule of the month (February 2001).

This must mean that insulin does what it does by folding into its specific shape, and bonding to receptors to cause cells to start absorbing glucose, etc.

That's it. I'm sure there are all sorts of complications in the details (about which I know nothing) but that is the idea in a nutshell. Cool!

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P.S. So, if only things that fit together in the proper fashion go on to 'react' then one can imagine that this 'lock and key' a couple of interesting issues come to mind: specificity and process control.

By specificity I mean that having a suficiently complicated 'lock' or receptor will restrict reaction to a very specific 'key' or substrate. This means that a biological process can be very picky about the things that react or perhaps less picky allowing more than one molecule to undergo the process.

By process control I mean that since a biological reaction requires that two specific molecules interact, one can control the reaction. For example, you could increase or decrease the reaction by adding or removing one or both of the two components. Or (more interestingly) you can speed or slow the reaction by adding more or less of a thrid molecule that fits in the lock but doesn't react or at least not in the same way! This idea of getting in the way is common in biology....cool, huh?

There are more things one mull over about but I'm tired and off to bed....

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http://www.physorg.com/news171812800.html

http://www.physorg.com/news171738311.html