Machine Learning Thermochemistry¶

This tutorial will teach you how to:

Download and install the ANI-1ccx machine learning (ML) potential parameter set 1 for organic molecules containing H, C, N, and O. ANI-1ccx was fitted to DLPNO-CCSD(T) reference data, which is a good approximation to CCSD(T).
Calculate a gasphase reaction energy for an isomerization reaction using ANI-1ccx.

Tip

Starting with AMS2024 you can also use AIMNet2 models in the ML potential engine.

The above reaction is part of the ISOL benchmark set 2 for organic isomerization reactions. The CCSD(T)-calculated reaction (isomerization) energy is +5.30 kcal/mol. 3

Set up and run ANI-1ccx calculations¶

You can set up and run the calculations for this tutorial using either the Graphical User Interface (GUI) or the python library PLAMS. First run the tutorial with the GUI, as that will install all necessary dependencies automatically.

Start AMSinput.
Switch to ML Potential:  → 
Set the Task to Single Point.
Set the Model to ANI-1ccx.
Import the coordinates for Molecule 1 (see below), either using File → Import system or by copy-pasting the coordinates into the AMSinput window.

Molecule 1 (download e_14.xyz) 2

26
IUPAC name: 1-(2-hydroxyphenyl)-2-methylbutane-1,3-dione, SMILES: CC(C(C)=O)C(=O)C1=CC=CC=C1O
C -3.24936 -0.212182 0.190882
C -3.01801 -0.0802601 1.55311
C -1.7187 0.143077 2.0465
C -0.658905 0.237377 1.15805
C -0.85036 0.110814 -0.240083
C -2.18086 -0.127187 -0.722042
C 0.257368 0.192893 -1.20091
O -2.46179 -0.277404 -2.02665
O 0.0637521 0.021523 -2.42106
C 1.687 0.513911 -0.736396
C 1.82965 1.96165 -0.236582
C 2.26431 -0.537731 0.241396
O 2.83801 -0.218511 1.26503
C 2.09562 -1.98435 -0.18481
H -4.2473 -0.390066 -0.201691
H -3.85485 -0.151744 2.24553
H -1.54519 0.241444 3.115
H 0.337705 0.411287 1.5486
H -1.5891 -0.204256 -2.50899
H 2.28669 0.397982 -1.65101
H 1.23053 2.14235 0.660044
H 1.50728 2.65825 -1.0195
H 2.87801 2.15978 0.0111843
H 2.38148 -2.11343 -1.23712
H 1.03194 -2.25389 -0.109562
H 2.68509 -2.64132 0.461071

6. Save the job with the name mol1singlepoint.ams.

7. If this is the first time you save a job with ANI-1ccx, you will be prompted whether to download and install the torchani backend. Select yes. It may take some time for the installation to complete. The installation requires a working internet connection.

If you are not prompted with the installation message, you can also open the SCM package manager using SCM → Packages, select TorchANI ML, and install.

8. Run the job: File → Run

9. Open the output file with AMSoutput: SCM → Output

Locate the energy in the section CALCULATION RESULTS:

CALCULATION RESULTS

Energy (hartree)          -651.36347065

Repeat the above steps for Molecule 2 (download p_14.xyz, or copy-paste the below coordinates)

26
IUPAC name: 2-propanoylphenyl acetate, SMILES: CCC(=O)C1=CC=CC=C1OC(C)=O
C -1.35638 2.12763 -0.654007
C -2.65222 1.75563 -0.292767
C -2.90548 0.454054 0.153058
C -1.86072 -0.467483 0.220499
C -0.53966 -0.111261 -0.111996
C -0.306066 1.21169 -0.548059
H -1.13871 3.125 -1.02877
H -3.46206 2.47839 -0.367275
H -3.9125 0.155448 0.435085
H -2.0661 -1.48038 0.55676
C 0.57311 -1.12022 -0.00101029
O 0.9385 1.6089 -1.01312
C 1.92817 2.11103 -0.153398
O 2.98828 2.39775 -0.635067
C 1.53429 2.27455 1.29711
O 1.68963 -0.797396 0.374748
C 0.239438 -2.56023 -0.391226
C 1.46196 -3.48021 -0.429606
H 0.619254 2.87262 1.3887
H 2.35794 2.7588 1.82629
H 1.34095 1.28633 1.72799
H -0.278681 -2.53555 -1.3614
H -0.505878 -2.93972 0.325436
H 2.19583 -3.11674 -1.15805
H 1.16125 -4.49774 -0.707814
H 1.95586 -3.51088 0.547894

The output for Molecule 2 should read

CALCULATION RESULTS

Energy (hartree)          -651.35251657

which gives a reaction energy of (-651.35251657)-(-651.36347065) = 0.010954 Hartree = +6.9 kcal/mol.

1. Download
e_14.xyz
and
p_14.xyz,
which correspond to molecules 1 and 2, respectively.
2. Save the below script with the name reaction.py.
3. Run the script using PLAMS: in a terminal, type $AMSBIN/plams reaction.py. It will print the reaction energy.
4. Your calculation results are saved in the plams_workdir/ directory.

In the following python script (using the PLAMS library) we set up two single-point calculations using the MLPotential engine with Model ANI-1ccx, and calculate the reaction energy.

s = Settings()
s.input.ams.Task = "SinglePoint"
s.input.MLPotential.Model = "ANI-1ccx"

job1 = AMSJob(name="mol1", settings=s, molecule=Molecule("e_14.xyz"))
job2 = AMSJob(name="mol2", settings=s, molecule=Molecule("p_14.xyz"))

job1.run()
job2.run()

E1 = job1.results.get_energy(unit="kcal/mol")
E2 = job2.results.get_energy(unit="kcal/mol")
deltaE = E2 - E1

print("Energy molecule 1: {:.2f} kcal/mol".format(E1))
print("Energy molecule 2: {:.2f} kcal/mol".format(E2))
print("Reaction energy  : {:.2f} kcal/mol".format(deltaE))

Note

It may take a few seconds to initialize the ANI-1ccx model, and in the above script it is initialized two times. If you have two or more identical single point or geometry optimization calculations for different molecules, consider running them via a PLAMS AMSWorker:

s = Settings()
s.input.MLPotential.Model = "ANI-1ccx"

molecules = {"molecule1": Molecule("e_14.xyz"), "molecule2": Molecule("p_14.xyz")}

with AMSWorker(s) as worker:
    E = dict()

    for name, mol in molecules.items():
        results = worker.SinglePoint(name, mol)
        E[name] = results.get_energy(unit="kcal/mol")
        print("Energy of {} = {:.2f} kcal/mol".format(name, E[name]))

    print("Reaction energy: {:.2f} kcal/mol".format(E["molecule2"] - E["molecule1"]))

With a PLAMS AMSWorker, you can run calculations for many molecules while only running the initialization once. That can save a lot of time for fast methods like ANI-1ccx.

Estimating reliability¶

Machine learning potentials give accurate predictions only for molecules or systems similar to those that were used during the parameterization of the machine learning potential. For other systems, the predictions may be very inaccurate.

The prediction (i.e., the energy, as calculated above) from the ANI potentials, like ANI-1ccx, are averages over 8 separately trained neural networks (a neural network ensemble). The standard deviation of the 8 separate predictions can be used as a measure for estimating how reliable a prediction is. If all predictions are very similar (small standard deviation), similar molecules to the calculated one should have appeared in the training set. If the predictions are very different (large standard deviation), then the potential has likely not been trained to the type of molecule it is being used for.

Starting with AMS2024, in the output you can additionally find a line “Energy uncertainty”. For example, for Molecule 1, you will see

Engine energy uncertainty (hartree)              0.00212839

In this case, the standard deviation for Molecule 1 is 2.128 mHa = 1.3 kcal/mol. For Molecule 2, it is 1.8 kcal/mol. It is up to you to decide whether you consider these numbers to be “small” (good) or “large” (bad). For more information, see for example Refs 1 and 4.

Note

The standard deviation grows with the square root of the number of atoms (assuming per-atom prediction errors follow a normal distribution). When comparing standard deviations for molecules with different number of atoms, it is a good idea to consider the standard deviation per sqrt(atom) shown above.

Free energies, vibrational normal modes, and more¶

The given structures had been optimized at a high level of theory. 2 You can also (re-)optimize them with ANI-1ccx:

Start AMSjobs.
Open the mol1singlepoint job with AMSinput.
Set the Task to Geometry Optimization.
Tick the Frequencies checkbox.
Save as mol1geo and run.

Look for Gibbs free energy in the output (see the Thermo keyword).

In AMSjobs select the mol1geo job.
Open it with the SCM → Output menu command.
In the search field at the bottom type ‘Gibbs’ and observe the Gibbs free energy.
Visualize the normal modes in AMSspectra: SCM → Spectra.

Tip

ANI-1ccx geometry optimization jobs can be run interactively in AMSinput. Right-click on the pre-optimizer button , and select ANI-1ccx.

Note

The reaction energy above was calculated for particular conformations of the molecules 1 and 2. To explore all conformational isomers (conformers), see the Conformers tutorial.

Tip

If your organic molecules contain F, S, and/or Cl, you can run calculations using the ANI-2x model.

Tip

Consider using ANI-1ccx or ANI-2x to calculate a full approximate Hessian, and then use ADF to refine the vibrational modes that interest you.

Tip

By default the ANI calculations will use all available cpu on your machine. To run a serial calculation, on the Details → Technical panel, set Number of threads to 1.

On the same panel, you can also choose to run calculations on a CUDA-enabled GPU. See the parallelization section of the MLPotential manual for more details.

References¶

1(1,2): J. S. Smith et al., Nat. Commun. 10 (2019) 2903. https://doi.org/10.1038/s41467-019-10827-4
2(1,2,3): R. Huenerbein et al. Phys. Chem. Chem. Phys. 12 (2010) 6940-6948. https://doi.org/10.1039/C003951A
3: S. Luo, Y. Zhao, D.G. Truhlar. Phys. Chem. Chem. Phys. 13 (2011) 13683-13689. https://doi.org/10.1039/C1CP20834A
4: J. S. Smith et al., J. Chem. Phys. 148 (2018) 241733. https://doi.org/10.1063/1.5023802