# Tutorial 04 - Optimizing Force Fields

In this tutorial we will be using the OpenFF Evaluator framework in combination with the fantastic ForceBalance software to optimize a molecular force field against the physical property data set we created in the first tutorial.

ForceBalance offers a suite of tools for optimizing molecular force fields against a set of target data. Perhaps one of the most fundamental targets to fit against is experimental physical property data. Physical property data has been used extensively for decades to inform the values of non-bonded Van der Waals (VdW) interaction parameters (often referred to as Lennard-Jones parameters).

ForceBalance is seamlessly integrated with the evaluator framework, using it to evaluate the deviations between target experimentally measured data points and those evaluated using the force field being optimized (as well as the gradient of those deviations with respect to the force field parameters being optimized).

The tutorial will cover:

• setting up the input files and directory structure required by ForceBalace.

• setting up an EvaluatorServer for ForceBalance to connect to.

• running ForceBalance using those input files.

• extracting and plotting a number of statistics output during the optimization.

Note: If you are running this tutorial in google colab you will need to run a setup script instead of following the installation instructions:

[1]:

# !wget https://raw.githubusercontent.com/openforcefield/openff-evaluator/master/docs/tutorials/colab_setup.ipynb
# %run colab_setup.ipynb


For this tutorial make sure that you are using a GPU accelerated runtime.

For the sake of clarity all warnings will be disabled in this tutorial:

[2]:

import warnings
warnings.filterwarnings('ignore')
import logging
logging.getLogger("openforcefield").setLevel(logging.ERROR)


We will also enable time-stamped logging to help track the progress of our calculations:

[3]:

from openff.evaluator.utils import setup_timestamp_logging
setup_timestamp_logging()


## Setting up the ForceBalance Inputs

In this section we will be creating the directory structure required by ForceBalance, and populating it with the required input files.

### Creating the Directory Structure

To begin with, we will create a directory to store the starting force field parameters in:

[4]:

!mkdir forcefield


and one to store the input parameters for our ‘fitting target’ - in this case a data set of physical properties:

[5]:

!mkdir -p targets/pure_data


### Defining the Training Data Set

With the directories created, we will next specify the data set of physical properties which we will be training the force field against:

[6]:

# For convenience we will use the copy shipped with the framework
from openff.evaluator.utils import get_data_filename
data_set_path = get_data_filename("tutorials/tutorial01/filtered_data_set.json")

from openff.evaluator.datasets import PhysicalPropertyDataSet
data_set = PhysicalPropertyDataSet.from_json(data_set_path)

# Due to a small bug in ForceBalance we need to zero out any uncertainties
# which are undefined. This will be fixed in future versions.
from openff.evaluator.attributes import UNDEFINED

for physical_property in data_set:

if physical_property.uncertainty != UNDEFINED:
continue

physical_property.uncertainty = 0.0 * physical_property.default_unit()


To speed up the runtime of this tutorial, we will only train the force field against measurements made for ethanol

[7]:

data_set.filter_by_smiles("CCO")


in real optimizations however the data set should be much larger than two data points!

With those changes made, we can save the data set in our targets directory:

[8]:

# Store the data set in the pure_data targets folder:
data_set.json("targets/pure_data/training_set.json");


### Defining the Starting Force Field Parameters

We will use the OpenFF Parsley 1.0.0 force field as the starting parameters for the optimization. These can be loaded directly into an OpenFF ForceField object using the OpenFF toolkit:

[9]:

from openforcefield.typing.engines.smirnoff import ForceField
force_field = ForceField('openff-1.0.0.offxml')


In order to use these parameters in ForceBalance, we need to ‘tag’ the individual parameters in the force field that we wish to optimize. The toolkit easily enables us to add these tags using cosmetic attributes:

[10]:

# Extract the smiles of all unique components in our data set.
from openforcefield.topology import Molecule, Topology

all_smiles = set(
component.smiles
for substance in data_set.substances
for component in substance.components
)

for smiles in all_smiles:

# Find those VdW parameters which would be applied to those components.
molecule = Molecule.from_smiles(smiles)
topology = Topology.from_molecules([molecule])

labels = force_field.label_molecules(topology)[0]

# Tag the exercised parameters as to be optimized.
for parameter in labels["vdW"].values():


Here we have made use of the toolkit’s handy label_molecules function to see which VdW parameters will be assigned to the molecules in our data set, and tagged them to be parameterized.

With those tags added, we can save the parameters in the forcefield directory:

[11]:

# Save the annotated force field file.
force_field.to_file('forcefield/openff-1.0.0-tagged.offxml')


Note: The force field parameters are stored in theOpenFF SMIRNOFF XML format.

### Creating the Main Input File

Next, we will create the main ForceBalance input file. For the sake of brevity a default input file which ships with this framework will be used:

[12]:

input_file_path = get_data_filename("tutorials/tutorial04/optimize.in")

# Copy the input file into our directory structure
import shutil
shutil.copyfile(input_file_path, "optimize.in")

[12]:

'optimize.in'


While there are many options that can be set within this file, the main options of interest for our purposes appear at the bottom of the file:

[13]:

!tail -n 6 optimize.in

$target name pure_data type Evaluator_SMIRNOFF weight 1.0 openff.evaluator_input options.json$end


Here we have specified that we wish to create a new ForceBalance Evaluator_SMIRNOFF target called pure_data (corresponding to the name of the directory we created in the earlier step).

The main input to this target is the file path to an options.json file - it is this file which will specify all the options which should be used when ForceBalance requests that our target data set be estimated using the current sets of force field parameters.

We will create this file in the targets/pure_data directory later in this section.

The data set is the JSON serialized representation of the PhysicalPropertyDataSet we created during the first tutorial.

### Defining the Estimation Options

The final step before we can start the optimization is to create the set of options which will govern how our data set is estimated using the Evaluator framework.

These options will be stored in an Evaluator_SMIRNOFF object:

[14]:

from forcebalance.evaluator_io import Evaluator_SMIRNOFF

# Create the ForceBalance options object
target_options = Evaluator_SMIRNOFF.OptionsFile()
# Set the path to the data set
target_options.data_set_path = "training_set.json"


This object exposes both a set of ForceBalance specific options, as well as the set of Evaluator options.

The ForceBalance specific options allow us to define how each type of property will contribute to the optimization objective function (the value which we are trying to minimize):

$\Delta(\theta) = \sum^N_n \dfrac{weight_n}{M_n} \sum^{M_n}_m \left(\dfrac{y_m^{ref} - y_m(\theta)}{denominator_{n}}\right)^2$

where $$N$$ is the number of types of properties (e.g. density, enthalpy of vaporization, etc.), $$M_n$$ is the number of data points of type $$n$$, $$y_m^{ref}$$ is the experimental value of data point $$m$$ and $$y_m(\theta)$$ is the estimated value of data point $$m$$ using the current force field parameters

In particular, the options object allows us to specify both an amount to scale each type of properties contribution to the objective function by ($$weight_n$$), and the amount to scale the difference between the experimental and estimated properties ($$denominator_n$$):

[15]:

from openff.units import unit

target_options.weights = {
"Density": 1.0,
"EnthalpyOfVaporization": 1.0
}
target_options.denominators = {
"Density": 30.0 * unit.kilogram / unit.meter ** 3,
"EnthalpyOfVaporization": 3.0 * unit.kilojoule / unit.mole
}


where here we have chosen values that ensure that both types of properties contribute roughly equally to the total objective function.

The Evaluator specific options correspond to a standard RequestOptions object:

[16]:

from openff.evaluator.client import RequestOptions

# Create the options which evaluator should use.
evaluator_options = RequestOptions()
# Choose which calculation layers to make available.
evaluator_options.calculation_layers = ["SimulationLayer"]

# Reduce the default number of molecules
from openff.evaluator.properties import Density, EnthalpyOfVaporization

density_schema = Density.default_simulation_schema(n_molecules=256)
h_vap_schema = EnthalpyOfVaporization.default_simulation_schema(n_molecules=256)

target_options.estimation_options = evaluator_options


These options allow us to control exactly how each type of property should be estimated, which calculation approaches should be used and more. Here we use the same options are were used in the second tutorial

And that’s the options created! We will finish off by serializing the options into our target directory:

[17]:

# Save the options to file.
with open("targets/pure_data/options.json", "w") as file:
file.write(target_options.to_json())


## Launching an Evaluator Server

With the ForceBalance options created, we can now move onto launching the EvaluatorServer which ForceBalance will call out to when it needs the data set to be evaluated:

[18]:

# Launch the calculation backend which will distribute any calculations.
from openff.evaluator.backends import ComputeResources

number_of_workers=1,
resources_per_worker=ComputeResources(
number_of_gpus=1,
preferred_gpu_toolkit=ComputeResources.GPUToolkit.CUDA
),
)
calculation_backend.start()

# Launch the server object which will listen for estimation requests and schedule any
# required calculations.
from openff.evaluator.server import EvaluatorServer

evaluator_server = EvaluatorServer(calculation_backend=calculation_backend)
evaluator_server.start(asynchronous=True)

01:30:20.505 INFO     Server listening at port 8000


We will not go into the details of this here as this was already covered in the second tutorial

## Running ForceBalance

With the inputs created and an Evaluator server spun up, we are finally ready to run the optimization! This can be accomplished with a single command:

[19]:

!ForceBalance optimize.in


If everything went well ForceBalance should exit cleanly, and will have stored out newly optimized force field in the results directory.

[20]:

!ls result/optimize

openff-1.0.0-tagged_1.offxml  openff-1.0.0-tagged.offxml


## Plotting the results

As a last step in this tutorial, we will extract the objective function at each iteration from the ForceBalance output files and plot this using matplotlib.

First, we will extract the objective function from the pickle serialized output files which can be found in the optimize.tmp/pure_data/iter_****/ directories:

[21]:

from forcebalance.nifty import lp_load

# Determine how many iterations ForceBalance has completed.
from glob import glob
n_iterations = len(glob("optimize.tmp/pure_data/iter*"))

# Extract the objective function at each iteration.
objective_function = []

for iteration in range(n_iterations):

folder_name = "iter_" + str(iteration).zfill(4)
file_path = f"optimize.tmp/pure_data/{folder_name}/objective.p"

objective_function.append(statistics["X"])

print(objective_function)

[0.9270359101845124, 0.011497456194198362]


The objective function is then easily plotted:

[22]:

from matplotlib import pyplot
figure, axis = pyplot.subplots(1, 1, figsize=(4, 4))

axis.set_xlabel("Iteration")
axis.set_ylabel("Objective Function")

axis.plot(range(n_iterations), objective_function, marker="o")

figure.tight_layout()


## Conclusion

And that concludes the fourth tutorial!

If you have any questions and / or feedback, please open an issue on the GitHub issue tracker.