Folding@home - Comparison To Other Molecular Simulators

Comparison To Other Molecular Simulators

Rosetta@home is a distributed computing project aimed at protein structure prediction and is one of the most accurate tertiary structure predictors. The conformational states from Rosetta's software can be used to initialize a Markov state model as starting points for Folding@home simulations. Conversely, structure prediction algorithms can be improved from thermodynamic and kinetic models and the sampling aspects of protein folding simulations. As Rosetta only tries to predict the final folded state, and not how proteins fold, Rosetta@home and Folding@home are complementary and address very different molecular questions.

Anton is a special-purpose supercomputer constructed for molecular dynamics simulations. In October 2011 Anton and Folding@home were the two most powerful molecular dynamics systems. Anton is unique in its ability to produce single ultra-long computationally expensive molecular trajectories, such as one in 2010 which reached the millisecond range. These long trajectories may be particularly helpful towards certain types of biochemical problems. However, Anton does not use Markov state models for analysis. In 2011 the Pande lab constructed a MSM from two 100-µs Anton simulations and found alternative folding pathways that were not visible through Anton's traditional analysis. They concluded that there was little difference between MSMs constructed from a limited number of long trajectories or one assembled from many shorter trajectories. In June 2011 Folding@home began additional sampling of an Anton simulation in an effort to better determine how its techniques compare to Anton's methods. However, unlike Folding@home's shorter trajectories, which are more amenable to distributed computing and other parallelization techniques, longer trajectories do not require adaptive sampling to sufficiently sample the protein's phase space. Due to this, it is possible that a combination of Anton's and Folding@home's simulation methods would provide a more thorough sampling of this space.