Molecular Dynamics - Design Constraints

Design Constraints

Design of a molecular dynamics simulation should account for the available computational power. Simulation size (n=number of particles), timestep and total time duration must be selected so that the calculation can finish within a reasonable time period. However, the simulations should be long enough to be relevant to the time scales of the natural processes being studied. To make statistically valid conclusions from the simulations, the time span simulated should match the kinetics of the natural process. Otherwise, it is analogous to making conclusions about how a human walks from less than one footstep. Most scientific publications about the dynamics of proteins and DNA use data from simulations spanning nanoseconds (10−9 s) to microseconds (10−6 s). To obtain these simulations, several CPU-days to CPU-years are needed. Parallel algorithms allow the load to be distributed among CPUs; an example is the spatial or force decomposition algorithm .

During a classical MD simulation, the most CPU intensive task is the evaluation of the potential (force field) as a function of the particles' internal coordinates. Within that energy evaluation, the most expensive one is the non-bonded or non-covalent part. In Big O notation, common molecular dynamics simulations scale by if all pair-wise electrostatic and van der Waals interactions must be accounted for explicitly. This computational cost can be reduced by employing electrostatics methods such as Particle Mesh Ewald ( ), P3M or good spherical cutoff techniques ( ).

Another factor that impacts total CPU time required by a simulation is the size of the integration timestep. This is the time length between evaluations of the potential. The timestep must be chosen small enough to avoid discretization errors (i.e. smaller than the fastest vibrational frequency in the system). Typical timesteps for classical MD are in the order of 1 femtosecond (10−15 s). This value may be extended by using algorithms such as SHAKE, which fix the vibrations of the fastest atoms (e.g. hydrogens) into place. Multiple time scale methods have also been developed, which allow for extended times between updates of slower long-range forces.

For simulating molecules in a solvent, a choice should be made between explicit solvent and implicit solvent. Explicit solvent particles (such as the TIP3P, SPC/E and SPC-f water models) must be calculated expensively by the force field, while implicit solvents use a mean-field approach. Using an explicit solvent is computationally expensive, requiring inclusion of roughly ten times more particles in the simulation. But the granularity and viscosity of explicit solvent is essential to reproduce certain properties of the solute molecules. This is especially important to reproduce kinetics.

In all kinds of molecular dynamics simulations, the simulation box size must be large enough to avoid boundary condition artifacts. Boundary conditions are often treated by choosing fixed values at the edges (which may cause artifacts), or by employing periodic boundary conditions in which one side of the simulation loops back to the opposite side, mimicking a bulk phase.