[22:11:25] Project: 5766 (Run 12, Clone 103, Gen 274)
[16:19:58] Project: 2653 (Run 1, Clone 160, Gen 139)
[22:46:35] Project: 5766 (Run 10, Clone 99, Gen 1421)
MtM wrote:Dan Ensign -> http://folding.stanford.edu/Pande/People
From what I understood from Dan's texts and pm's at the time ( he wrote those articles in 'laymans' terms so we donors could try and understand them ) F@H does simulate the waiting time between transitions. That was the whole point of F@H, enter starting values into a simulation model and let it run, basically a coin flip where the chances of seeing an actual transition is very very slim. I am not sure if F@H has already found enough transitional states to only research variations on those starting values, but I can imagine this is only partially true?
I don't understand what you mean with 'the first to cross the free-energy barrier wins'. Clone's are made because F@H does not know what forces and start positions are needed to get a protein to fold, so clone's are made to simulate a larger range within a single Run ( group with same atom placement, temperature ect but with different velocities as mentioned in the wiki article ). Clone's are almost identical but differ in their initial molecular movement. Tbh I asked Dan why velocities and temperature was different, as the speed of which molecules move depend on their temperature from my understanding, but it was to hard to explain to someone without the background needed so I couldn't tell you/anyone this either as I don't know for sure. It might have to do with what you mentioned, explicit and implicit models. In one model, there are no forces to be considered except the forces between the molecules of the protein. In the other, there is a solvent which interacts with them as well. Maybe the article, since it was made before implicit solvent models were available to F@H, mentioned clones this way because they couldn't simulate the effects of a solvent's interaction with the molecules other then giving them different initial directions of movement, but I'm guessing here.
The generations are based on simulation length, or steps. If x steps have been reached the work unit is finished and sent in, and a new work unit can be given out continuing from the last state of that previous work unit.
As I just said, I'm not sure clones in implicit solvent models being the same, maybe they still need to stimulate variances in initial directions and speeds of molecules and it still applies.
Not a very satisfactory answer maybe, and I'm surely hoping someone who is a molecular dynamics expert to answer your questions but I thought I'd share what came to mind reading your post.
I gather that they figure out the related conformation states first, then the WUs figure out the rates of transition between them.
MtM wrote:I am not an expert, but this sounds really wrong to me.I gather that they figure out the related conformation states first, then the WUs figure out the rates of transition between them.
To me it reads like you're saying that the simulation is done from a folded to denatured state, when to my knowledge it is the other way around?
In layman's term ( sorry ) I believe that clone's are needed to cover a range of possible initial movement (direction/speed) for each individual atom, and that any of them could potentially lead to a transitional state and then a folded state. I don't know, for reasons given, why this direction/speed isn't specified by temperature ( well I have a hunch, temperature might relate more directly to speed of movement, but can't predict direction as those will vary due to interactions with other forces ( 'random start direction' followed by movement of atoms directed by attraction or repulsion to other molecules or solvents based on electron count(?) and to some extent maybe gravity(?) ect?? ).
gwildperson wrote:I remember reading another layman's explanation that bruce wrote quite some time back. I don't know if it was on this website or the older version that died. It made sense at the time and the two explanations together were better than either one.
gwildperson wrote:I did some thinking about this earlier today, trying to explain FAH to my brother over our Thanksgiving dinner so it's fresher in my mind than it would otherwise be.
gwildperson wrote:Every project starts out with the atoms in particular positions. It may be a completely denatured or at some intermediate state. I think it can run "backwards" depending on the initial energy, either folding or unfolding.
Not only must positions be assumed, initial velocity and direction must be assumed. Starting from different positions or with different velocities will probably create different runs and/or clones.
Jesse_V wrote:Right, but I thought the PG group only studied unfolded (either partially or fully) => folded.
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