Step 9

The final step in the set-up process is to equilibrate the solvated system. There is no unique way to do this but a general procedure would be to perform a series of molecular dynamics simulations in which the heavy atoms of the protein are harmonically tethered by tethering forces that are gradually decreased to zero. This is unnecessary here as a similar method was employed in Step 8 when solvating the protein. Instead, here, a single molecular dynamics simulation is performed:

# . Parameters.

_Steps = 10000

# . Get the system with no fixed atoms and an appropriate NB model.

system = Unpickle ( "step8_b.pkl" )

system.Summary ( )

# . Define a normal deviate generator in a given state.

normalDeviateGenerator = NormalDeviateGenerator.WithRandomNumberGenerator ( RandomNumberGenerator.WithSeed ( 511717 ) )

# . Dynamics.

LangevinDynamics_SystemGeometry ( system ,

collisionFrequency = 25.0 ,

logFrequency = 100 ,

normalDeviateGenerator = normalDeviateGenerator ,

steps = _Steps ,

temperature = 300.0 ,

timeStep = 0.001 )

# . Save the system.

Pickle ( "step9.pkl", system )

For the purposes of illustration, 10 ps of Langevin (NVT) dynamics are performed here. In actual applications, however, equilibration might require significantly longer simulations, and it may also be preferable to use alternative sampling algorithms, such as NPT dynamics or even Monte Carlo. Likewise, some studies will require modifications to the above procedure. Thus, for example, a hybrid potential investigation of an enzyme reaction would probably involve a partial pre-equilibration using a MM potential before finishing off with simulations with a QC/MM energy model.