Molecular dynamics (MD) simulations provide a computational microscope that lets you watch how a molecule moves over time.
MD works by calculating the forces that result from the interactions between atoms (e.g. electrostatic attraction and repulsion, interatomic van der Waals interactions, bonded interactions). These forces are calculated for every atom in each molecule in a molecular system, and used to work out how each atom would move over time. The result is a molecular dynamics trajectory, which can be used to produce a movie that approximates the motion of the complete biomolecular system.
DIfferent levels of coarse-graining: from quantum to mesoscopic. These relate to length and time scales.
Different water models.
Bond, angle, torsion, improper dihedral, van der Walls, electrostatic, ..
the particle mesh Ewald algorithm (PME). This is the clever algorithm that allows each periodic image to interact electrostatically with the infinite number of other periodic images. All simulations that use periodic boundary conditions should turn on PME.
Note that the periodic boundary condition doesn't change the fact that a simulation where the (unit) volume is constant is a microcanonical ensemble. This is because the conditions required for the microcanonical ensemble are satisfied: the particle number, energy, and volume of the system are conserved (again, where the system is the unit volume, which we are simulating). If you think about it, reflecting boundary conditions and periodic b.c.s are not so different. The periodic one is just like the reflecting + teleportation to the opposite wall!
If we want to control the pressure, we need to use a barostat. Again, there are many different barostat algorithms available, with the choice of barostat normally coupled with the choice of thermostat. The best barostat to use for biomolecular simulations is namd is the “Langevin” barostat. This randomly changes the volume of the periodic box, and can be switched on by adding the following lines to ‘mdconfig’
Amber tools has many tools useful for MD simulations
Tutorial for using GROMACS for MD: link
Meta-dynamics: bias the dynamics (using some descriptor coordinates), so that we explore the configuration space more. We then compute the free energy of the explored space by taking into account this bias.
These calculations can be used to guide Drug discovery