Happy Birthday Prokaryote

[Synthohol]

:bday: :bday: Best wishes dude!!:bday: :bday:

[sptw]

Happy Birthday Prokaryote :bday:

[Ruantic]

Happy Birthday Prokaryote

[Farabomb]

Happy b-day m8 :bday: :drinkbud:

[amdrules770]

happy b-day dude. getting folding machines as presents??? ;)

[notoriousformula]

hey Prokaryote, HAPPY BIRTHDAY man :bday: :balloons: :bgpressy: :birthday: :party: :bash4: :present: :cake:

notor :P

[Drake]

Have a good one, Prok! :bgpressy:

[WesM63]

Happy B-Day M8. Have a good one!!

[nitan]

Happy birthday dude...have a good one...:drinky:

[prokaryote]

Thanks everyone!

Yeah, I got folding machines for the old B-day! :rolleyes: :D

Just what I wanted!

[mdzcpa]

Happy Bday M8! Sorry for being a bit late:)

[speculative]

Hope you had a great birthday. :) :djsmiles:

-spec

[amdrules770]

If you got more folding machines, then what happened to your foldin production? lol :D

[prokaryote]

Originally posted by amdrules770
If you got more folding machines, then what happened to your foldin production? lol :D


hehehe, they're a-folding of a different color (DF under "bacillus" to help give Team LiquidNinja a boost for a bit, so technically they're still folding :D. Though I still stand by my earlier conviction that the phase II methodology is really no different than the phase I methodology, only now instead of looking at random single points, they're looking at random "dimples" in the folding space energy topology... better, but not nearly up to the potential of using evolutioinary mechinisms operating on genetic algorithms... maybe phase XXX? :rolleyes: ).

[Synthohol]

Hang on, let me get my degree in SAYWHAT??:D :D :D

[prokaryote]

:D okay, it was jargon filled. If you know what I was talking about then forgive the long winded explanation below.

Let's see if I can explain how I think that DF is doing this protein structure thing.

Let's pretend that the protein we care about is only composed of 3 amino acids, call them Larry, Curly and Moe. :D

Since there's only 3 of them then no matter how they are arranged, they can fit on a table top (3 points determine a plane).

Draw a graph coordinate system on the table top (X axis and Y axis)

Put Moe at the intersection of the two axes (the point (0,0)) and call this point the origin.

Since we've fixed the location of Moe relative to the X and Y axes we can now specify a position of Larry and Curly relative to Moe.

Say Larry is 3 units to the right of Moe and 1 unit up (3,1) and Curly is 4 units to the right of Moe and 3 units up (4,2).

When Larry, Curly and Moe are in this arrangement, there is a certain amount of force necessary to hold them there. DF is somehow translating this force or bond energies for each amino acid to a distance measurement in Angstroms and finding what the standard deviation of all of them are (that would be the RMSD or root mean square distance value that is shown). Let's say that they have a value of 10 Angstroms in this arrangement.

What phase I of DF did was pick random placements (within some given biochemical constraints such as Larry could only be next to Moe and Curly in a somewhat straight line say) of Larry Curly Moe and about 100 of their friends and calculated the RMSD for that arrangement. It did this for each structure that it randomly picked or generated.

Back to Larry, Curly and Moe. This is kind of a hard part. We're going to create a 6 dimensional surface in a 7 dimensional hypercube that will represent the energy for each possible arrangement of Larry, Curly and Moe.

I guess the best way to describe this is to use a 3D example. Lets say that each arrangement of the stooges can be mapped to one spot on another table top. In other words when Moe is at (0,0), Larry is at (3,1) and Curly is at (4,2) in the first table top, we'll arbitrarily assign this configuration to the spot (1,1) on this new graph, but now we're going to add one more dimension, height above the table that represents the RMSD value. Imagine that there's a sheet of very stretchable plastic suspended above the table and we have a ruler demarked in units of RMSD. So at the table top point of (1,1) we push down on the sheet at this point until it is at 10 units of RMSD above the table and stays there. Now do this for every possilbe arrangement of the stooges.

That deformed plastic sheet is the energy surface. What DF was trying to do was find the lowest point on the entire surface. This lowest point would be associated with the lowest amount of energy that is required to hold Larry, Curly and Moe in a particular arrangement. In nature, proteins naturally want to be at this lowest energy state. Therefore, the shape of the protein (the arrangement of Larry, Curly and Moe) at this point is most likely going to be the way a protein will end up after it has folded.

The best or lowest RMSD points for each different protein are what was submitted to the CASP5 contest. DF did okay (about middle of the pack).

Back to the 6 dimensional surface in a 7 dimensional hyper cube. In reality, the arrangement of Larry, Curly and Moe can be describe by just stringing together all of the coordinate numbers along with the RMSD number into one long vector with 7 places (0, 0, 3, 1, 4, 2, 10). The first 6 numbers are the table top coordinates for the stooges and represent a 6 dimensional surface (One wierda$$ table). The 7th number is the energy or how high above the table this one arrangement of the stooges is located and is what gives the 6D surface it's bumpiness. It really is the same as our 3D example above, just that no-one can imagine what a 6 dimenional surface looks like!

Okay that was DF phase I. Just a bunch of random points sampled on our bumpy surface.

For DF II, what I believe is going on is that initially (generation 0), 10,000 points are picked at random and their energy is measured (the same as in DF I).

Only now, the lowest energy structure is picked. By the use of a genetic algorithm, the area around this point is explored and a lower energy state structure is returned (it would be the structure associated with the lowest energy state found within this region around the best structure from generation 0). So instead of exploring random points, we're exploring random dimples (the area instead of the point).

My gripe with this method is that it is fundamentally no different than DF phase I, only instead of a point we're now using a small area. One thing to remember is that the energy surface area is enormous and even by expanding points to areas, we're not even coming close to exploring a majority of the energy surface area.

What I think should have been done is as follows:

Step one, carry out the same calculations as is done in DF phase II.

Step two, report back the 50 structures from generation 250 for every person.

Step three, add these 50 structures to a population or database of "good" structures, say the top 1,000,000.

Step four, when you work on your next 250 generations, the generation 0 is not randomly generated, instead 50 individuals or structures are chosen from the population of 1,000,000 good structures and you continue evolving these through to generation 250. This employs a variation of the concept of evolutionary theory called punctuated equilibrium (where, in this case, the perturbation to a genetically stable isolated population is the introduction of new members from another population that has also evolved in isolation).

Step 5, repeat steps 2 through 4 until no further appreciable improvement in RMSD is found.

The benefit to this method is that the space between isolated dimples can also be explored.

Or so I think, but I could just be full of @#$%. :D :D :D

prok

[dicki]

:eek: good explanation (i think!)

happy birthday...