Molecular dynamic simulation is a technique to study structure-to-function relationship of macromolecules, mimicking real-life motion of atoms and molecules. MD is now a well accepted and widely used technique to get into the bottom of protein structures and dynamics to study ligand binding, problems related to protein denaturation, enzyme reaction mechanisms and protein re-folding. But its accuracy and reliability depends on the quality of the force field employed to model the intra- and intermolecular interactions.
In terms of biophysics, the basic theory of protein folding says, “the protein spontaneously assumes the conformation of lowest energy for a given environment” and simulation is nothing but the representation of the energy of the protein as a function of its atomic coordinates. The most populated states at thermal equilibrium are expected to be those with low potential energy function and forces acting on the individual atoms are related to the gradient of this function, commonly termed as “force fields”.
A force field is a mathematical expression describing the dependence of the energy of a system on the coordinates of its particles, consisting of an analytical form of the interatomic potential energy and a set of parameters. The parameters are typically obtained either from ab-initio or semi-empirical quantum mechanical calculations or by fitting to experimental data such as neutron, X-ray and electron diffraction, NMR, infrared, Raman and neutron spectroscopy, etc.The most popular force fields used in MD are AMBER, CHARMM, GROMOS and OPLS.
AMBER is the acronym for Assisted Model Building with Energy Refinement and it is parameterized mainly for proteins and nucleic acids, CHARMM (Chemistry at HARvard Macromolecular Mechanics) was originally designed for the protein and nucleic acid but now it can be applied to a range of biomolecules, molecular dynamics, solvation, crystal packing, vibrational analysis and QM/MM studies. OPLS (Optimized Potentials for Liquid Simulations) was the third main development in the early 1980’s, build to simulate liquid state properties, initially for water and for more than 40 organic liquids. GROMOS (GROningen MOlecular Simulation) force field was optimized with respect to the condensed phase properties of alkanes.
GROMACS, which is one of the best available software package for MD, does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. It is a fast, flexible, open source software and have applications in membrane simulation, membrane protein simulation, interaction of molecules with ionizing x-rays, combined quantum mechanics and classical mechanics, protein folding related simulation.
References:
1). González, M. A. “Force fields and molecular dynamics simulations.” École thématique de la Société Française de la Neutronique 12 (2011): 169-200.
2). Van Der Spoel, David, Erik Lindahl, Berk Hess, Gerrit Groenhof, Alan E. Mark, and Herman JC Berendsen. “GROMACS: fast, flexible, and free.” Journal of computational chemistry 26, no. 16 (2005): 1701-1718.
3). Ponder, Jay W., and David A. Case. “Force fields for protein simulations.” In Advances in protein chemistry, vol. 66, pp. 27-85. Academic Press, 2003.