	This is part of the maze module
	It is only available if you configure PLUMED with ./configure –enable-modules=maze . Furthermore, this feature is still being developed so take care when using it and report any problems on the mailing list.

Calculates the biasing direction along which the ligand unbinds by minimizing the MAZE_LOSS function. The optimal biasing direction is determined by performing simulated annealing.

Description of components

By default this Action calculates the following quantities. These quantities can be referenced elsewhere in the input by using this Action's label followed by a dot and the name of the quantity required from the list below.

Quantity	Description
x	Optimal biasing direction; x component.
y	Optimal biasing direction; y component.
z	Optimal biasing direction; z component.
loss	Loss function value defined by the provided pairing function.
sr	Sampling radius. Reduces sampling to the local proximity of the ligand position.

The atoms involved can be specified using

LIGAND	Indices of ligand atoms.. For more information on how to specify lists of atoms see Groups and Virtual Atoms
PROTEIN	Indices of protein atoms.. For more information on how to specify lists of atoms see Groups and Virtual Atoms

Compulsory keywords

N_ITER	Number of optimization steps. Required only for optimizers, do not pass this keyword to the fake optimizers (results in crash) , e.g., random walk, steered MD, or random acceleration MD.
OPTIMIZER_STRIDE	Optimizer stride. Sets up a callback function that launches the optimization process every OPTIMIZER_STRIDE.
PROBABILITY_DECREASER	Temperature-like parameter that is decreased during optimization to modify the Metropolis-Hastings acceptance probability.
COOLING	Reduction factor for PROBABILITY_DECREASER, should be in (0, 1].
COOLING_SCHEME	Cooling scheme: geometric.

Options

NUMERICAL_DERIVATIVES	( default=off ) calculate the derivatives for these quantities numerically
NOPBC	( default=off ) ignore the periodic boundary conditions when calculating distances
SERIAL	( default=off ) Perform the simulation in serial – used only for debugging purposes, should not be used otherwise.
PAIR	( default=off ) Pair only the 1st element of the 1st group with the 1st element in the second, etc.
NLIST	( default=on ) Use a neighbor list of ligand-protein atom pairs to speed up the calculating of the distances.
NL_CUTOFF	Neighbor list cut-off for the distances of ligand-protein atom pairs.
NL_STRIDE	Update stride for the ligand-protein atom pairs in the neighbor list.
LOSS	Loss function describing ligand-protein interactions required by every optimizer.

Examples

Every optimizer implemented in the maze module needs a loss function as an argument, and it should be passed using the MAZE_LOSS keyword.

In the following example simulated annealing is launched for 1000 iterations as the optimizer for the loss function every 200 ps. The geometric cooling scheme is used.

UNITS LENGTH=A TIME=ps ENERGY=kcal/mol

MAZE_SIMULATED_ANNEALING ...
  LABEL=sa

  LOSS=l

  N_ITER=1000
  OPTIMIZER_STRIDE=200

  PROBABILITY_DECREASER=300
  COOLING=0.95
  COOLING_TYPE=geometric

  LIGAND=2635-2646
  PROTEIN=1-2634
... MAZE_SIMULATED_ANNEALING

As shown above, each optimizer should be provided with the LIGAND and the PROTEIN keywords.