docking

Though a bit drier than the above mentioned type of docking (dry-dock? ouch ...), docking in computational chemistry is the endeavor of determining how two molecules interact. Molecular interactions are the key to nearly all biological process. proteins, regulating gene transcription. Metals bind to DNA and proteins, affecting structure and function. Hormones bind to receptor proteins on cells, triggering cell responses.

The challenge in docking is determing the most stable way two molecules interact. If you take a lock and key analogy, the docked complex would be the key inserted in the lock. If you're talking about a protein and a horomone, however, the best fit is less obvious. Various computational methods have attacked this problem by trying to define the relative surfaces of the two interacting parties. Then, depending on parameters in a force field, you sample over different interactions until the best one is found.

This sort of technology is coveted by pharmaceutical companies, who are always looking for new drugs to interact with specfic proteins. If they have a way of screening potential drugs on a computer before actually synthesizing them and doing drug trials, it can save a lot of money.

There are several different approaches to docking, based either on the philosophy of molecular dynamics - where the ligand is essentially allowed to wander around in space until it finds the binding site - or on a more exhaustive search concept. Two current programs are:

• FtDock : good for protein-protein interactions.
• AutoDock : more receptor-ligand searching.

The FtDock (fourier transform dock) moves one set of protein coordinates through the other - imagine the points representing the atoms of one chain plotted on tracing paper and moved through small steps across a plot of the other chain. Except, of course, in 3D.

Where the points collide, a high value results; and where they don't, a low value is recorded. This builds up a map of possible interfaces for each run - where a single 'run' is one orientation of the moving protein. For as many orientations as the step size demands, best positions for the moving molecule are produced and the list is sorted to produce a best overall position / orientation.

For AutoDock, the algorithm is quite different (as well as very complicated). The ligand is first 'gridded' against the receptor - that is, for each point on a 3D grid over the protein the energy of each ligand atom is computed and stored in a grid map. For a typical CHO ligand (sucrose, say) four grid maps are produced - C, H, O and e (electrostatics). These are used too speed up the docking.

The actual procedure is to randomly move from a starting point (which is specified by the ligand's initial coordinates) random changes to its position and orientation are made. Two different search techniques can be used: lamarkian genetic algorithms or simulated annealing, which both do essentially the same thing of selection of the best positions from a random population. The latter approach uses a temperature, which cools during the run.

Docking is also a pseudo-veterinary procedure (not all vets will do it, you really don't need a vet to do it) performed on some animals, in which a variable length of the animal's tail is cut off, usually when the animals is just a few days old.

For dogs, the procedure has its origins in the neccecities of hunting- a dog with a long tail had more (relatively) unneccessary appenditure to get tangled up in underbrush, and so the tail would be removed. Currently, a number of breeds of dog must have their tails docked in order to be shown as per American Kennel Club regulations. Note: dogs use their tails to communicate, cutting their tails off is at least partially akin to cutting off a human's tongue.

For cows, docking was originally performed for hygienic reasons, as disease would spread from cow to dairy worker when a cow got urine on its bushy-tipped tail, flicked its tail around, and got small amounts of urine into the eyes of some poor guy sitting and milking on a low stool. Currently some but not all cows are docked. Sheep are still usually docked in order that their very wooly tails not collect feces and harbor maggots.

See cropping.

slipping one partner's foreskin over the glans penis of another. right on!!