Once upon a time in a previous career I saw an eminent biochemist give a seminar on how enzymes work. Enzymes are those little catalytic dynamos that do the heavy chemical processing in biological systems. Our livers and guts, for example host many enzymes and their job is to neutralize any foreign substances that we consume as well as to breakdown foodstuffs to give us energy.
The guy was well past retirement age, but he had only recently turned to computer modeling to solve some questions that had nagged him his entire career. What he had turned to relatively late was the modelling of reactions
in silico, a term meant to distinguish it from experiments
in vitro and
in vivo. Modelling complex things i
n silico (like the weather for example) has taken a hit in the public eye lately, but this guy was smart enough to know the pitfalls of his own techniques.
Now I don't have the time to explain how enzymes work but part of the theory is the so-called lock and key model:
The multicolored molecule on the right is a substrate (the key) and the thing under it is an enzyme (lock). The lock and key metaphor comes from the very specific fit between the substrate and enzyme so that other keys can't fit the lock. There are very specific reasons why we wouldn't want other keys to fit. Getting back to the seminar, the general topic was how to model the lock and key model for a particular enzyme and substrate.
A typical substrate molecule is not a very static thing. If I could animate the cartoon above, the substrate would be flip-flopping and rotating, and generally moving every which way. So how does an enzyme get a substrate molecule to fit the lock? The stock answer is that the substrate is held in place and then induced to react by a mixture of different chemical "forces" available to the enzyme: electrostatic, hydrophobic, hydrogen bonding, etc. These little cumulative forces "pin down" a substrate. But the gist of the speaker's news was that it's not a matter of making sure that the substrate orients or lines up in preferred conformation; rather, it's a matter of expending enough energy to
prevent a substrate from doing many motions and gyrations that it would otherwise do in the absence of the enzyme. That might be a subtle point but I grasped it immediately because it struck a chord with work I had previously done.
After the lecture I approached the older man at a wine & cheese mixer, introduced myself, and explained how I had worked with some very special kinds of solvents (called liquid crystals) which are able to get much smaller molecules dissolved in them to line up. Turns out that the orientation occurs not because the smaller molecules are attracted to the larger molecule but rather because they are
prevented from adopting certain conformations- i.e., their freedoms are restricted (but not completely of course). The old man smiled and told me that I may have been the only other person in the room who "got" what he had been trying to say earlier.
Later on I thought about a non-technical way to explain the same thing. Being the father of a toddler, I likened it to how a parent watches over a toddler,
preventing the child from doing certain things which it might otherwise do given limitless options. Watching over a small child is often not instilling in the child to do the right things but rather restricting its choices--herding if you will.
