LTMD: Key new technology for accelerating folding and misfolding simulations in FAH

[PcPerf bot]

Here's an update one one of our key projects looking into protein folding, performed in collaboration with Prof. Jesus Izaguirre's lab at Notre Dame.  Below is an update from Prof. Izaguirre on the progress of this project.

 

The Izaguirre Lab at the University of Notre Dame (http://www.nd.edu/~lcls) has been collaborating with the Pande Lab at Notre Dame to produce a new GPU core that leverages the amazing speed of OpenMM implicit-solvent force calculations (the heart of the GPU core in Folding@home) with new Long Timestep Molecular Dynamics (LTMD). This combination currently allows nearly a 10-fold speedup over OpenMM for systems as small as the WW domain (35 residues, 544 atoms) up to the Lambda repressor (80 residues, 2000 atoms). This translates into about 10 microseconds per day of simulation, which brings single trajectory millisecond simulations closer to FAH. 

 

In collaboration with Cauldron Development (lead by Joseph Coffland, primary developer of the Folding@home client and also some cores), we hope to produce a GPU core that might be the first hybrid CPU-GPU core. There are technical questions on how to best do this, and we will engage our enthusiastic beta-tester GPU donors to discuss how to best approach this core when we are closer to production mode. 

 

Going forward, we will continue to improve the LTMD GPU technology to obtain larger speedups for ever larger and biomedically relevant systems. A particularly excitement development will be the extension of LTMD GPU technology to explicit solvent simulations. 

 

As far as scientific simulations, we are simulating the folding of about 80 mutants of the Pin1 WW domain, a protein implicated in some cancers and Alzheimer's disease. Understanding the role of mutations on misfolding can have important biomedical consequences, since many diseases have at least some component of misfolding of proteins. Another exciting project we are about to start is to simulate the dimerization during folding of proinsulin and proinsulin mutants, which results in some types of Type IA young and adult onset diabetes. 

 

Thanks to the FAH donors, testers, and to the Pande Lab for their generosity and leadership which has allowed our technological developments and simulations to come this far. 

 

 

 

 

An image of the Pin WW domain.

 

 

 

 

 

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