Folding@Home - Binding of a Ligand (small molecule drug) to Proteins

Stanford University Biotechnology Dept ^ | Jan 03, 2008 | Peter Kasson

[texas booster]

We're often interested in comparing things--predicting a known difference is a good way to test our methods. Then, once we're pretty confident that things work, we want to predict ways to change the way proteins interact. Changing a system in a defined way is both a good tool for biological insight and the basis for a lot of medical treatments.

In this particular case, we're interested in the "selectivity" of ligand binding by a protein: the protein is known to bind one small molecule ("ligand") much better than another. So project 3903/3905 is a pair of projects comparing the protein-small molecule interactions, one project for each small molecule. Project 3906/3907 are the essential "control" projects that tells us how different the small molecules are in the way that they interact with the water around them. When we combine these pairs of projects, we can then calculate the difference between the "bound" state in which the protein is interacting with the small molecule and the "unbound" state in which the protein and small molecule each just interact with the environment. There are experimental data on the difference between these two small molecules; if we get good results here, we'll go on to test a number of interactions that aren't experimentally known yet.

The trick is that some protein-small molecule interactions are quite easy to test experimentally and some are very hard. Using Folding@Home, they are all moderate in difficulty. So if we can validate our methods on the "easy" ones, we can then predict the "hard" ones. Usually only a small fraction of protein-small molecule interactions that one tests turn out to be important. For the ones we predict are really interesting, we can do the experiment. But Folding@Home allows us to skip the experiments that are both hard and likely not to be interesting. This sounds simple, but it can be very powerful in trying to understand the underlying biology.

We also hope that it can help us understand a number of diseases and drug interactions better. For instance, a number of diseases or "failures" of medical therapy are due to mutations in proteins (changes to their amino acid sequence). We would like to understand how these mutations affect the interactions between the protein and the drug. If we can understand that, we can help suggest ways to improve the drug therapy. This is obviously a large, hard problem, but we think that Folding@Home can play an important role here.

[LearnsFromMistakes]

I am already set up and folding...but I have 2 cores and I am only using 1 to fold (when I am not gaming). Can I get both going and get more work done? I thought that is what the instructions were for...

[antiRepublicrat]

When’s the Mac SMP client coming out? It’s still an expired beta.

[agooga]

I fold for my parents, and all those who suffer. We can win!

[antiRepublicrat]

Think we can goad DU into producing more? Their rank is down at 192, with us at 54. Rub their noses in their failure to help their fellow man as opposed to the uncaring conservatives who are contributing about three times as much every day, seven times as much total.

It’ll only mean more towards curing disease if they take on the challenge.

[Drango]

Fold one for the Gipper bump.

[EasySt]

Warner goes Blu-ray exclusive!
This means the Blu-Ray versus HD-DVD format war is all but over.

HD-DVD fanboy meltdown, imminent... PS3 Folders rejoice!

Probably the best way to do Blu-Ray right now is with a Sony PlayStation 3.

$399 buys a 40GB PlayStation 3 with a built in Blu-Ray player. (This model uses the new low power consumption chip set.) The PS3 is Internet connected via Ethernet or wireless, can stream movies and music from your PC, plays games at up to 1080P, upscales and upconverts your existing DVDs nicely and its Internet network is free. (Unlike X-Box Live...)

The PlayStation 3's Operating System, along with its Blu-Ray player’s firmware, are easily updated from the Internet so the player is, and will remain, up to date with the current Blu-Ray Specification.

Also included as an option in the PlayStation 3 Operating System is Stanford’s “Folding at Home” application for performing distributed computing protein folding science to find cures for misfolded protein deseases like Alzheimer's and Parkinson’s, etc. when your PS3 isn’t being used to play movies or games. (Good for around 900+ F@H points per day...)

[texas booster]

Check the name of your F@H folder. It is probably in C:\Program Files\F@H.

Make a second directory, say F@H 2, and copy the F@H console into it.

Run as Administrator the program following the previous instructions and you should be set.

To verify, press Cntl-Alt-Del to open the Task Manager. If you see two F@H consoles running at around 50%, then you are running two F@H kernals, one on each core.

[LearnsFromMistakes]

Just took a few minutes to unload the previous and load this up. 2 cores up and running. How much more electricity am I gonna use now??? Sounds like I just fired up the jet...

[texas booster]

Your energy usage will increase some.

It sounds like the CPU fan just kick in full time. Might want to consider blowing it out with some canned air.

[texas booster]

Congrats to all new folders showing up this weekend.

See your points here:

http://folding.extremeoverclocking.com/user_list.php?s=&a=2&t=36120

[texas booster]

Thankfully school is back in session!

Glad to have all of your contribution back full strength.

[ThomasThomas]

I heard that you could put a OS on the playstation3. So I purchased one to try putting Linux on it. Do you know anything about this? Is there anyway to put a usb keyboard on it? When I’m not playing with it is faster than my other computers combined at folding.

[EasySt]

You can plug a regular USB keyboard and even a USB mouse into the PS3. I did, and it was simple plug and play. You can even plug a USB2 powered hub into it, to get more ports.

I have not put Linux on either of my PS3s but I've read that it can be done, in fact, people have connected eight PS3's together with a gigabit switch and run a version of Linux on them all, making a 200 Giga-flop supercomputer...

http://blogs.zdnet.com/storage/?p=220

http://gravity.phy.umassd.edu/ps3.html

Here's a link about installing Fedora Linux on a PS3: PS3-install-instructions-for-Fedora-Core-5

More links can be found in this thread: http://www.freerepublic.com/focus/f-chat/1930299/posts



Happy Folding!

[texas booster]

Wow, 139,000 points for the last 24 hours, as of 7:30 AM CST.

Thanks to Klutz and all of the other folders in FReeper land!

http://folding.extremeoverclocking.com/team_summary.php?s=&t=36120

[HKMk23]

I JUST set up a second instance of the console version on my Dual Core box here at the office (running XP Pro, SP2), so I'll lay out for you exactly what I just finished doing. With any luck at all, you should have success. Now, I'm running the 5.02 core, and I wouldn't expect that you'd have vastly different results doing this with the 5.03 or 5.04 cores, but -- just in case -- I'll make that disclosure right up front, here.

To begin with, I already had one instance running as a service out of one directory. Taking a look at the "Processes" tab in Task Manager would show me the currently executing FAH Core happily sucking up 50% of my CPU usage.

Taking a look at the Services Control panel (Start > Control Panel > Administrative Tools > Services OR Start > Run... and type services.msc), I could see a service named "FAH@C:+<directory name>+FAH502-Console.exe", where <directory name> is the directory on my C: drive where the console executable resides that I had running already.

I created a second directory, and copied the console and core executables to that new directory.

I ran services.msc and stopped the one core that had been running.

I then ran the console executable out of the NEW directory using the -configonly switch.

During that configuration, I answered "yes" when asked if I wanted the console to run as a service. I also answered "yes" to configure advanced options, so I could set the Machine ID = 2.

At that point, I had two separate folders with two separate client.cfg files. The only differences between them were that the original CFG has MachineID=1, and the new CFG file in the new directory has MachineID=2, and the old CFG also had an entry "local=256" which does not appear in the new CFG file.

With all of that completed, I held my breath, and restarted my computer.

BOTH instances of FAH started independently, running as two distinct, differently-named services in the Services control panel, the original instance continued right where it left off with the WU it already had, and the new instance downloaded its first WU and began crunching away.

I hope you achieve results that are at least that satisfactory.

[texas booster]

Discussion over here on a potential reversal for Alzheinmer’s Disease:

http://www.freerepublic.com/focus/news/1951040/posts

[Freedom2specul8]

Marked to read...

[texas booster]

In the animation above “Inner Life of a Cell” there is a segment discussing the building of microtubules in a cell, and motor proteins that “walk” on these microtubules to carry proteins across a cell.

The U of Pennsylvania has published an important study showing how the motor proteins actually connect and disconnect.

http://www.freerepublic.com/focus/f-news/1955604/posts

Some of the research that is being done on F@H computers may one day reach that goal of finding a cure for Alzheimer’s Disease and many others.

Please check out the link. It is a terrific discovery!

[neverdem]

Thanks for the ping.

[Bellflower]

ping