Molecular Dynamics - Examples of Applications

Examples of Applications

Molecular dynamics is used in many fields of science.

• First MD simulation of a biological process was published in 1976. Its simulation published in Nature paved the way for understanding protein motion as essential in function and not just accessory.

• First MD simulation of a simplified biological folding process was published in 1975. Its simulation published in Nature paved the way for the vast area of modern computational protein-folding.

• MD is the standard method to treat collision cascades in the heat spike regime, i.e. the effects that energetic neutron and ion irradiation have on solids an solid surfaces.

• MD simulations were successfully applied to predict the molecular basis of the most common protein mutation N370S, causing Gaucher Disease. In a follow-up publication it was shown that these blind predictions show a surprisingly high correlation with experimental work on the same mutant, published independently at a later point.

The following two biophysical examples are not run-of-the-mill MD simulations. They illustrate notable efforts to produce simulations of a system of very large size (a complete virus) and very long simulation times (500 microseconds):

• MD simulation of the complete satellite tobacco mosaic virus (STMV) (2006, Size: 1 million atoms, Simulation time: 50 ns, program: NAMD) This virus is a small, icosahedral plant virus which worsens the symptoms of infection by Tobacco Mosaic Virus (TMV). Molecular dynamics simulations were used to probe the mechanisms of viral assembly. The entire STMV particle consists of 60 identical copies of a single protein that make up the viral capsid (coating), and a 1063 nucleotide single stranded RNA genome. One key finding is that the capsid is very unstable when there is no RNA inside. The simulation would take a single 2006 desktop computer around 35 years to complete. It was thus done in many processors in parallel with continuous communication between them.

• Folding simulations of the Villin Headpiece in all-atom detail (2006, Size: 20,000 atoms; Simulation time: 500 µs = 500,000 ns, Program: Folding@home) This simulation was run in 200,000 CPU's of participating personal computers around the world. These computers had the Folding@home program installed, a large-scale distributed computing effort coordinated by Vijay Pande at Stanford University. The kinetic properties of the Villin Headpiece protein were probed by using many independent, short trajectories run by CPU's without continuous real-time communication. One technique employed was the Pfold value analysis, which measures the probability of folding before unfolding of a specific starting conformation. Pfold gives information about transition state structures and an ordering of conformations along the folding pathway. Each trajectory in a Pfold calculation can be relatively short, but many independent trajectories are needed.