Folding@home

Meet FAH team member: Greg Bowman

I wanted to continue the series of introducing FAH team members.  Greg Bowman has been a key figure in FAH the last few years, especially in methods and software development and its applications to protein folding (eg see the list of software he's made available on Simtk.org).

Here's a short intro written by Greg to tell his personal story.

Between the second and third grades I lost most of my vision due to a protein misfolding disease called juvenile macular degeneration (JMD).  At the time, I was too young to understand the full implications of my disorder; however, they became abundantly clear during middle school.  I soon learned that JMD is the result of a few point mutations in a key gene I’d inherited from my parents and, therefore, took a keen interest in exciting developments in molecular biology like the cloning of Dolly the sheep as they pointed to a means of curing diseases like my own. 

A pressing challenge was then to discover how to make a contribution to molecular biology, given that performing laboratory experiments is extremely challenging with poor vision.  Fortunately, I developed a passion for computer science and mathematical modeling during high school and realized that these skills could be brought to bear on biological problems.  To prepare myself for a career in biological computing, I completed a major in computer science and minors in biomedical engineering and chemistry at Cornell University, where I also began basic research on protein folding.

Now I am performing full-time research on protein folding and misfolding in the Pande lab.  While I have not been able to tackle JMD directly at this point, I have developed methods that will be critical for doing so and begun working on other protein misfolding diseases like Alzheimer’s.

 

10 Years

While it's not directly a major milestone for FAH, it's something very relevant for me:  July 1 was my 10th year anniversary at Stanford.  It's amazing that 10 years has gone by, in some ways quickly and in some ways not.  I do recall fondly the "old days" when my lab was just me and a small number of students, although that time was pretty tough in many ways.  It's nice to have the key academic life issues past (tenure, etc).

But, this is not the relevant 10 year mark for most:  FAH's 10 year mark.  That too is coming up, on October 1, 2010.  That's only about a year away and we're been thinking about some special things we can do to celebrate that very important milestone.

Meet FAH team member Jason Wagoner

Jason Wagoner is a relatively new member of the FAH team, but has already made some critically important contributions. Jason has already done a great deal of research relevant to Folding@home, when he was an undergraduate at Washington University at St Louis, working in Nathan Baker's lab.  Jason's work centers around understanding water, and how water interacts with proteins.  In particular, Jason is an expert in developing models for water which (we hope) will be more accurate, faster than existing models, AND well suited to architectures such as the PS3 or GPU.  Jason has been working with Dr. Edgar Luttmann (see previous post about Edgar) on this new water model, and we're hoping to have our first paper submitted for peer review soon (maybe 1-2 weeks).

Meet FAH team member Dr. Vince Voelz

Dr. Vince Voelz is a relatively recent addition to the Folding@home team.  His interests involve studying protein folding in biophysical settings as well as folding in the presence of the ribosome.  He is part of the multi-institutional grant from NSF's Frontiers In Biological Research program.  While it's a bit early to talk about his work with FAH, Vince has been one of the key driving force behind a major new protein folding initiative at Folding@home (more on that later) as well as working with FIBR experimentalists to see what we can do to predict their experiments and build a tighter connection in general.

Below is a recent youtube movie where Vince explains about electrostatics in proteins, a key aspect of protein stability.
 

Meet FAH team member Dr. Edgar Luttmann

Dr. Edgar Luttmann has been a FAH group member for several years.  His primary areas of interest are Alzheimer's Disease and new methods for describing water.  In studying Alzheimer's disease, Edgar has contributed to FAH in several ways.  He's been performing simulations of protein aggregation involved in Alzheimer's disease as well as helping understand the experimental work coming from the group (primarily NMR).

In his second research area, Edgar has been working with Jason Wagoner in the Pande group to develop better models of water.  These models were originally conceived in order to have a model which was more computationally efficient, but turns out that they may be both faster (by about 10x perhaps in some cases, maybe more) but also it looks like they may be in fact more accurate as well.  Finally, these new models are also very well suited to GPU's and PS3's.  Bottom line, we're very excited about this and hopefully will be submitting our first results for peer review soon.

Meet FAH team member Adam Beberg

While Adam Beberg is currently a grad student at Stanford in the Computer Science department and a member of the FAH team and Pande group, Adam has been collaborating with FAH from the very beginning.  Adam has experience with distributed computing beyond FAH, as he was one of he founders of distributed.net and from his experiences with that, wrote the Cosm library to help with many areas, including writing distributed computing code.

In his thesis work, Adam has worked in many areas, including distributed storage (more on that later), distributed computing code, as well as the GPU code.  For now, I'll highlight on his work with GPU's (and will comment on the rest at a later date).  Adam has helped make major steps forward in our FAH code for GPUs, taking the code from "academic quality" to something which is very robust and could be broadly useful.  This was a major undertaking, requiring knowledge in many areas including both the science, internals of GPUs, and the whole tool chain.  With Mark Friedrichs (a programmer in the Simbios center and Pande group), our GPU code is looking great and we hope to be making some major announcements soon (although it's too early to talk about more details now).

Meet FAH team member Dr. John Chodera

Dr. Chodera joined the lab about a year ago after completing his PhD at UCSF in Ken Dill's lab.  John plays a role in many projects in Folding@home, but I'll highlight two primary projects today. 

First, with former FAH team member Nina Singhal (now a professor at University of Chicago), John has further developed a new way  to use distributed computing to simulate long timescale dynamics.  This is at the very heart of how FAH works, so this is a very exciting advance for us.  The basic idea is to build a kinetic model of the long timescale process by diving the system into a series of states and calculating the transition probability between these states via molecular dynamics.  To make all of this possible requires some nifty statistics (especially a fair amount of Bayesian statistics, which is becoming more and more important to how we do our work).  The upshot is that we should now be able use FAH to do calculations which we couldn't do before, which is very exciting for us and hopefully will have a big impact on the broader scientific community as well.

Second, John has been working to further develop methods to calculate free energies, especially those relevant for biomolecules such as protein-ligand free energies.  These types of calculations are particularly relevant for our plans for late stages drug design, but also represent a major advance in computational methodology in general.

Meet FAH team member Paula Petrone

Since I'm on the topic of the ribosome, let me talk a bit about another group member working on the ribosome: Paula Petrone.  Paula's background is physics and biophysics.  Her work in FAH has been involved in two areas:  1) developing new ways to significantly speed FAH MD simulations with larger time step integration and 2) studies of the ribosome, understanding the chemical nature of the ribosome tunnel (discussed in the last few posts).  Her work sheds light on what proteins and antibiotics would see in the tunnel.  Along the way, she's made a very interesting discovery in her simulations, which could have a big impact on our understanding of how the ribosome works.  We're awaiting peer review on that paper and I'll give more details once the paper is further along.  This project is joint with other ribosomers in the group (Del Lucent -- previously highlighted -- and now former FAH team member Chris Snow).

Meet FAH team member Relly Brandman

Relly Brandman is a graduate student in the Chemical and Systems Biology Department at Stanford.  This department was originally called the Molecular Pharmacology Department and it still has a tradition of being very closely connected to pharmaceuticals and therapeutics.  Relly's work with Folding@home is very much in this tradition. 

Relly is interested in studying the ribosome tunnel as a target for novel antibiotics. There are already several antibiotics which target the ribosome tunnel (you may have already taken some, such as Erythromycin).  However, these drugs appears to be easily circumvented by the bacteria -- they have evolved around the drugs and have become drug resistant.  Indeed, drug resistance in bacteria makes sense -- as the drugs we take exit our bodies in urine, and sit in the sewers where they interact with bacteria.  The bacteria which survive are the ones that aren't affected, and this causes a selective pressure towards antibiotic resistance -- evolution at work!

Relly's project (joint with Guha Jayachandran, featured in a previous post) is to first predict and understand existing antibiotic behavior, and then predict novel antibiotics.  This is part of a Stanford University BioX grant, with two experimental groups.  If successful, we should be able to find novel types of antibiotics, which should hopefully be very useful in dealing with the major problem of drug resistance.

Meet FAH team member Dan Ensign

Dan Ensign joined the group two years ago and has quickly become a key member of the Folding@home team.  Dan's work centers around one of the core scientific areas in the group: understanding how proteins fold.  Dan is using all possible tools at his disposal, including regular FAH clients, SMP clients, GPU clients, and PS3 clients.  Dan's first paper using SMP clients just got accepted for publication and I'll highlight it in a little more detail below (but it really deserves its own post, which I'll leave for another date).  He is now turning a lot of attention to the analysis of all the piles and piles of data for the PS3 client and especially to work to continue to improve the calculations that are done on the PS3.  Indeed, his results were key in our scneitific improvements from v1.1 to v1.2 (current version).

Dan's work with SMP clients has lead to a phenomenal data sets for protein folding, including trajectories that are both large in number and very long.  This data set (which most people may have thought would be impossible to simulate) will play a key role in both understanding how small proteins fold, as well as in developing methods to further push FAH to study more and more complex proteins (as well as related questions such as misfolding and lipid vesicle fusion) by making more enhanced MSM methods.

Dan's work is pretty wide spread so I will likely make some more posts about it in the future.  For now, I'll leave you with a link to a youtube video where Dan's discussing some of the science behind FAH.