Combined Force-Frequency Sampling¶
Introduction¶
Combined Force-Frequency (CFF) sampling is a free energy sampling method which uses artificial neural networks to generate an on-the-fly adaptive bias capable of rapidly resolving free energy landscapes. It is a recent method proposed in [20], and its extension and application to ab initio MD has been demonstrated in [14]. The method’s main strength resides in its ability to learn both from the frequency of visits to distinct states and the generalized force estimates that arise in a system as it evolves in phase space. This is accomplished by introducing a self-integrating artificial neural network, which generates an estimate of the free energy directly from its derivatives.
CFF algorithm proceeds in sweeps. Statistics are collected over a user specified interval
(sweep), which is a very flexible choice. At the end of each sweep artificial neural
networks are fit to the statistics to determine the optimal bias which is then applied in
the subsequent sweep. This proceeds until the free energy landscape has converged.
Example Input¶
"methods" : [
{
"type" : "CFF",
"topology" : [12,8],
"nsweep" : 10000,
"temperature" : 298.15,
"grid" : {
"lower" : [-3.14159,-3.14159],
"upper" : [3.14159,3.14159],
"number_points" : [30,30],
"periodic" : [false,false]
},
"lower_bounds" : [-5,-5],
"upper_bounds" : [5,5],
"lower_bound_restraints" : [0.0,0.0],
"upper_bound_restraints" : [0.0,0.0],
"timestep" : 0.001,
"unit_conversion" : 1,
"minimum_count" : 3000,
"overwrite_output": true
}
]
Warning
Be sure to follow correct JSON syntax for your input, with a comma after every line except the last within each bracket.
Options & Parameters¶
Define CFF
In the methods block, define the CFF method through the syntax:
"type" : "CFF",
To define neural network topology:
"topology" : [12,8],
Array of integers (length: number of hidden layers). This array defines the architecture of the neural network. Like ANN Sampling, good heuristics is to use a network with a single hidden layer if you are biasing on one CV, and two hidden layers if you are biasing on two or more.
"temperature" : 298.15,
The temperature of the simulation must be specified.
To define the length of each sweep:
"nsweep" : 10000,
Typical values range from 1,000 to 10,000 depending on the size of the system. The slower the system dynamics, the longer the sweep. This is not going to heavily affect convergence time, and the method is generally quite robust to choice of sweep length. The main consequence of this choice is that the neural network training time becomes relatively expensive if the system’s free energy is very cheap to evaluate.
Define the grid
To define the bounds:
"lower" : [-3.14159,-3.14159],
"upper" : [3.14159,3.14159],
These are arrays of doubles whose length is the number of CVs used. This defines the minimum and maximum values for the CVs for the range in which the method will be used in order.
To define the number of CV bins used:
"number_points" : [30,30],
This array of integers defines the number of histogram bins in each CV dimension in order.
"periodic" : [false,false],
This array defines whether a given CV is periodic for restraint purposes. This is only
used to apply minimum image convention to CV restraints. The value can be safely set to
false even for periodic CVs if no restraints are being used.
Define the restraints
"lower_bounds" : [-5,-5],
"upper_bounds" : [5,5],
These arrays define the minimum and maximum values for the CV restraints in order.
"lower_bound_restraints" : [0,0],
"upper_bound_restraints" : [0,0],
These arrays define the spring constant for the lower and upper bounds.
Define time and unit parameters
"timestep" : 0.001,
The timestep of the simulation. Units depend on the conversion factor that follows. This must be entered correctly, otherwise the generalized force estimate will be incorrect.
"unit_conversion" : 1,
Defines the unit conversion from d(momentum)/d(time) to force for the simulation. For LAMMPS using units real, this is 2390.06 (gram.angstrom/mole.femtosecond^2 -> kcal/mole.angstrom). For GROMACS, this is 1.
"minimum_count" : 3000,
This is the number of hits required to a bin in the general histogram before the full
biasing force is active. Below this value, the bias linearly decreases to zero at
hits = 0. Default value is 200, but user should provide a reasonable value for
their system.
Handle outputs (Optional)
"overwrite_output" : [true],
If this is enabled, output files are overwritten at each sweep such. Otherwise, output
files are saved at each sweep. Default, true.
Output¶
There are six output files from this method: CFF.out, F_out, netstate.net,
netstate.net2, CFF.out_gamma, and traintime.out.
The main output of this method is stored in CFF.out. Each column corresponds
respectively to the CVs, visit frequencies (histogram), bias based on frequency-based ANN,
bias based on force-based ANN, average bias, and the average free energy estimate (which
is the negative of the average bias with a constant shift). The format is as follows:
cv1 cv2 ... hist bias(freq_only) bias(force_only) bias(avg) free_energy(avg)
A file called CFF.out_gamma outputs network complexity term gamma for each neural
net and the ratio of gammas from both neural nets. (See [20] for more
information.) The format is as follows:
sweep_iter gamma(freq_only) gamma(force_only) gamma_ratio
File traintime.out contains CPU wall time (in seconds) taken for training of neural
networks during each sweep.
Files called netstate.dat and netstate2.dat contain the neural network parameters
for each of the two neural networks used to apply biases during the sampling
(netstate.dat stores frequency-based parameters, while netstate2.dat stores
force-based ones). For more information about these files, see the ANN Sampling Method.
A file called F_out contains the Generalized Force vector field, which is the same
output file as the Adaptive Biasing Force method. Vectors defined on each point on a grid
that goes from CV_lower_bounds to CV_upper_bounds of each CV in its dimension, with
CV_bins of grid points in each dimension. The printout is in the following format: 2*N
number of columns, where N is the number of CVs. First N columns are coordinates in CV
space, the N+1 to 2N columns are components of the Generalized Force vectors. See the ABF
Sampling Method for more information.
An example of CFF (e.g., alanine dipeptide in water) is located in Examples/User/CFF/ADP.