Replacing explicit water and membrane molecules in molecular dynamics simulation to boost simulation speed

Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are not accessible by experimental methods(Lindahl, 2008). By now, many biologically relevant processes for drug design, toxicological studies and other fields of application, can not be performed by atomistic MD simulations (Lindahl, 2008).
In MD, the necessary time effort for carrying out a simulation is considerable and depends mainly on (1) the complexity of the simulated system (2) the simulated time scale (3) the simulation method (4) the efficiency of used hardware and software algorithms. Carried out MD simulations nowadays may still take weeks of calculation on high end computers.

In practice, biologically relevant processes, as e.g. protein folding, take usually place above the time scale of milli seconds. They can take up to the order of some thousands of seconds (in case of the folding of membrane proteins). Molecular dynamics computer simulations have reached the scale of micro seconds for simulations of systems where each atom was described and simulated over time.(Lindahl, 2008)

Nevertheless, MD has risen to an important promoter methodology for many different fields of application. By replacing bunches of atoms by artificial particles, complexity of the systems can be reduced. This method is called the coarse grain method (CG). Biggin and Bond (2008) found an acceleration of their simulation processes for self assembling membrane / protein systems in water by factor 100. They estimated one to two days of calculation for a simulated time scale of 0.1 to 0.2 micro seconds for their systems.

Implicit force fields like "IMPALA", aim to describe water and/or membrane molecules in simulations by a couple of simple and partially precalculable equations. “IMPALA” is a force field initially developed by our laboratory. Using this method, thousands of water and lipid molecules can be replaced, leading to a reduced complexity of the system to be simulated.
"IMPALA"(Ducarme et al., 1998) based on the assumption of rigid peptides and aimed to find the insertion characteristics of such in membranes. Elimination of the necessity for simulating the aqueous and lipid phase atom by atom in the software package "Gromacs"(Berendsen et al., 1995) will permit both: a gain of speed, as it was already the case for the introduction of the coarse grain method, and a gain of precision by turning rigid molecules flexible through "Gromacs". Our current work is the integration of the "IMPALA" implicit force field into "Gromacs".

Biggin, P.C. & Bond, P.J. Molecular dynamics simulations of membrane proteins. Methods Mol. Biol. 443, 147-60(2008).
Berendsen, et al. (1995) Comp. Phys. Comm. 91: 43-56.
Ducarme, P., Rahman, M. & Brasseur, R. IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30, 357-71(1998).
Lindahl, E.R. (2008). Molecular dynamics simulations. Methods Mol. Biol. 443, 3-23.