SchNet: A continuous-filter convolutional neural

network for modeling quantum interactions

K. T. Schütt1∗, P.-J. Kindermans1 , H. E. Sauceda2 , S. Chmiela1

A. Tkatchenko3 , K.-R. Müller1,4,5†
1
Machine Learning Group, Technische Universität Berlin, Germany
2
Theory Department, Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin, Germany
3
Physics and Materials Science Research Unit, University of Luxembourg, Luxembourg
4
Max-Planck-Institut für Informatik, Saarbrücken, Germany
5
Dept. of Brain and Cognitive Engineering, Korea University, Seoul, South Korea
∗
kristof.schuett@tu-berlin.de † klaus-robert.mueller@tu-berlin.de

Abstract
Deep learning has the potential to revolutionize quantum chemistry as it is ideally
suited to learn representations for structured data and speed up the exploration
of chemical space. While convolutional neural networks have proven to be the
first choice for images, audio and video data, the atoms in molecules are not
restricted to a grid. Instead, their precise locations contain essential physical
information, that would get lost if discretized. Thus, we propose to use continuous-
filter convolutional layers to be able to model local correlations without requiring
the data to lie on a grid. We apply those layers in SchNet: a novel deep learning
architecture modeling quantum interactions in molecules. We obtain a joint model
for the total energy and interatomic forces that follows fundamental quantum-
chemical principles. Our architecture achieves state-of-the-art performance for
benchmarks of equilibrium molecules and molecular dynamics trajectories. Finally,
we introduce a more challenging benchmark with chemical and structural variations
that suggests the path for further work.

1 Introduction
The discovery of novel molecules and materials with desired properties is crucial for applications
such as batteries, catalysis and drug design. However, the vastness of chemical compound space
and the computational cost of accurate quantum-chemical calculations prevent an exhaustive explo-
ration. In recent years, there have been increased efforts to use machine learning for the accelerated
discovery of molecules and materials with desired properties [1–9]. However, these methods are
only applied to stable systems in so-called equilibrium, i.e., local minima of the potential energy
surface E(r1 , . . . , rn ) where ri is the position of atom i. Data sets such as the established QM9
benchmark [10] contain only equilibrium molecules. Predicting stable atom arrangements is in itself
an important challenge in quantum chemistry and material science.
In general, it is not clear how to obtain equilibrium conformations without optimizing the atom
positions. Therefore, we need to compute both the total energy E(r1 , . . . , rn ) and the forces acting
on the atoms
∂E
Fi (r1 , . . . , rn ) = − (r1 , . . . , rn ). (1)
∂ri
One possibility is to use a less computationally costly, however, also less accurate quantum-chemical
approximation. Instead, we choose to extend the domain of our machine learning model to both
compositional (chemical) and configurational (structural) degrees of freedom.

31st Conference on Neural Information Processing Systems (NIPS 2017), Long Beach, CA, USA.
In this work, we aim to learn a representation for molecules using equilibrium and non-equilibrium
conformations. Such a general representation for atomistic systems should follow fundamental
quantum-mechanical principles. Most importantly, the predicted force field has to be curl-free.
Otherwise, it would be possible to follow a circular trajectory of atom positions such that the energy
keeps increasing, i.e., breaking the law of energy conservation. Furthermore, the potential energy
surface as well as its partial derivatives have to be smooth, e.g., in order to be able to perform geometry
optimization. Beyond that, it is beneficial that the model incorporates the invariance of the molecular
energy with respect to rotation, translation and atom indexing. Being able to model both chemical
and conformational variations constitutes an important step towards ML-driven quantum-chemical
exploration.
This work provides the following key contributions:

• We propose continuous-filter convolutional (cfconv) layers as a means to move beyond

grid-bound data such as images or audio towards modeling objects with arbitrary positions
such as astronomical observations or atoms in molecules and materials.
• We propose SchNet: a neural network specifically designed to respect essential quantum-
chemical constraints. In particular, we use the proposed cfconv layers in R3 to model
interactions of atoms at arbitrary positions in the molecule. SchNet delivers both rotationally
invariant energy prediction and rotationally equivariant force predictions. We obtain a
smooth potential energy surface and the resulting force-field is guaranteed to be energy-
conserving.
• We present a new, challenging benchmark – ISO17 – including both chemical and confor-
mational changes3 . We show that training with forces improves generalization in this setting
as well.

2 Related work
Previous work has used neural networks and Gaussian processes applied to hand-crafted features to
fit potential energy surfaces [11–16]. Graph convolutional networks for circular fingerprint [17] and
molecular graph convolutions [18] learn representations for molecules of arbitrary size. They encode
the molecular structure using neighborhood relationships as well as bond features, e.g., one-hot
encodings of single, double and triple bonds. In the following, we briefly review the related work that
will be used in our empirical evaluation: gradient domain machine learning (GDML), deep tensor
neural networks (DTNN) and enn-s2s.

Gradient-domain machine learning (GDML) Chmiela et al. [19] proposed GDML as a method
to construct force fields that explicitly obey the law of energy conservation. GDML captures the
relationship between energy and interatomic forces (see Eq. 1) by training the gradient of the energy
estimator. The functional relationship between atomic coordinates and interatomic forces is thus
learned directly and energy predictions are obtained by re-integration. However, GDML does not
scale well due to its kernel matrix growing quadratically with the number of atoms as well as the
number of examples. Beyond that, it is not designed to represent different compositions of atom
types unlike SchNet, DTNN and enn-s2s.

Deep tensor neural networks (DTNN) Schütt et al. [20] proposed the DTNN for molecules that
are inspired by the many-body Hamiltonian applied to the interactions of atoms. They have been
shown to reach chemical accuracy on a small set of molecular dynamics trajectories as well as QM9.
Even though the DTNN shares the invariances with our proposed architecture, its interaction layers
lack the continuous-filter convolution interpretation. It falls behind in accuracy compared to SchNet
and enn-s2s.

enn-s2s Gilmer et al. [21] proposed the enn-s2s as a variant of message-passing neural networks that
uses bond type features in addition to interatomic distances. It achieves state-of-the-art performance
on all properties of the QM9 benchmark [21]. Unfortunately, it cannot be used for molecular dynamics
predictions (MD-17). This is caused by discontinuities in their potential energy surface due to the
3
ISO17 is publicly available at www.quantum-machine.org.

2
Figure 1: The discrete filter (left) is not able to capture the subtle positional changes of the atoms
resulting in discontinuous energy predictions Ê (bottom left). The continuous filter captures these
changes and yields smooth energy predictions (bottom right).

discreteness of the one-hot encodings in their input. In contrast, SchNet does not use such features
and yields a continuous potential energy surface by using continuous-filter convolutional layers.

3 Continuous-filter convolutions

In deep learning, convolutional layers operate on discretized signals such as image pixels [22, 23],
video frames [24] or digital audio data [25]. While it is sufficient to define the filter on the same
grid in these cases, this is not possible for unevenly spaced inputs such as the atom positions of a
molecule (see Fig. 1). Other examples include astronomical observations [26], climate data [27]
and the financial market [28]. Commonly, this can be solved by a re-sampling approach defining
a representation on a grid [7, 29, 30]. However, choosing an appropriate interpolation scheme is
a challenge on its own and, possibly, requires a large number of grid points. Therefore, various
extensions of convolutional layers even beyond the Euclidean space exist, e.g., for graphs [31, 32]
and 3d shapes[33]. Analogously, we propose to use continuous filters that are able to handle unevenly
spaced data, in particular, atoms at arbitrary positions.
Given the feature representations of n objects X l = (xl1 , . . . , xln ) with xli ∈ RF at locations
R = (r1 , . . . , rn ) with ri ∈ RD , the continuous-filter convolutional layer l requires a filter-generating
function
W l : RD → RF ,
that maps from a position to the corresponding filter values. This constitutes a generalization of a
filter tensor in discrete convolutional layers. As in dynamic filter networks [34], this filter-generating
function is modeled with a neural network. While dynamic filter networks generate weights restricted
to a grid structure, our approach generalizes this to arbitrary position and number of objects. The
output xl+1
i for the convolutional layer at position ri is then given by
X
xl+1
i = (X l ∗ W l )i = xlj ◦ W l (ri − rj ), (2)
j

where "◦" represents the element-wise multiplication. We apply these convolutions feature-wise
for computational efficiency [35]. The interactions between feature maps are handled by separate
object-wise or, specifically, atom-wise layers in SchNet.

4 SchNet

SchNet is designed to learn a representation for the prediction of molecular energies and atomic
forces. It reflects fundamental physical laws including invariance to atom indexing and translation, a
smooth energy prediction w.r.t. atom positions as well as energy-conservation of the predicted force
fields. The energy and force predictions are rotationally invariant and equivariant, respectively.

3
Figure 2: Illustration of SchNet with an architectural overview (left), the interaction block (middle)
and the continuous-filter convolution with filter-generating network (right). The shifted softplus is
defined as ssp(x) = ln(0.5ex + 0.5).

4.1 Architecture

Fig. 2 shows an overview of the SchNet architecture. At each layer, the molecule is represented atom-
wise analogous to pixels in an image. Interactions between atoms are modeled by the three interaction
blocks. The final prediction is obtained after atom-wise updates of the feature representation and
pooling of the resulting atom-wise energy. In the following, we discuss the different components of
the network.

Molecular representation A molecule in a certain conformation can be described uniquely by a set

of n atoms with nuclear charges Z = (Z1 , . . . , Zn ) and atomic positions R = (r1 , . . . rn ). Through
the layers of the neural network, we represent the atoms using a tuple of features X l = (xl1 , . . . xln ),
with xli ∈ RF with the number of feature maps F , the number of atoms n and the current layer l. The
representation of atom i is initialized using an embedding dependent on the atom type Zi :
x0i = aZi . (3)
The atom type embeddings aZ are initialized randomly and optimized during training.

Atom-wise layers A recurring building block in our architecture are atom-wise layers. These are
dense layers that are applied separately to the representation xli of atom i:

xl+1
i = W l xli + bl
These layers is responsible for the recombination of feature maps. Since weights are shared across
atoms, our architecture remains scalable with respect to the size of the molecule.

Interaction The interaction blocks, as shown in Fig. 2 (middle), are responsible for updating the
atomic representations based on the molecular geometry R = (r1 , . . . rn ). We keep the number of
feature maps constant at F = 64 throughout the interaction part of the network. In contrast to MPNN
and DTNN, we do not use weight sharing across multiple interaction blocks.
The blocks use a residual connection inspired by ResNet [36]:

xl+1
i = xli + vil .

As shown in the interaction block in Fig. 2, the residual vil is computed through an atom-wise layer,
an interatomic continuous-filter convolution (cfconv) followed by two more atom-wise layers with a
softplus non-linearity in between. This allows for a flexible residual that incorporates interactions
between atoms and feature maps.

4
 (a) 1st interaction block (b) 2nd interaction block (c) 3rd interaction block

Figure 3: 10x10 Å cuts through all 64 radial, three-dimensional filters in each interaction block of
SchNet trained on molecular dynamics of ethanol. Negative values are blue, positive values are red.

Filter-generating networks The cfconv layer including its filter-generating network are depicted
at the right panel of Fig. 2. In order to satisfy the requirements for modeling molecular energies,
we restrict our filters for the cfconv layers to be rotationally invariant. The rotational invariance is
obtained by using interatomic distances

dij = kri − rj k

as input for the filter network. Without further processing, the filters would be highly correlated since
a neural network after initialization is close to linear. This leads to a plateau at the beginning of
training that is hard to overcome. We avoid this by expanding the distance with radial basis functions

ek (ri − rj ) = exp(−γkdij − µk k2 )

located at centers 0Å ≤ µk ≤ 30Å every 0.1Å with γ = 10Å. This is chosen such that all distances
occurring in the data sets are covered by the filters. Due to this additional non-linearity, the initial
filters are less correlated leading to a faster training procedure. Choosing fewer centers corresponds
to reducing the resolution of the filter, while restricting the range of the centers corresponds to the
filter size in a usual convolutional layer. An extensive evaluation of the impact of these variables is
left for future work. We feed the expanded distances into two dense layers with softplus activations
to compute the filter weight W (ri − rj ) as shown in Fig. 2 (right).
Fig 3 shows 2d-cuts through generated filters for all three interaction blocks of SchNet trained on
an ethanol molecular dynamics trajectory. We observe how each filter emphasizes certain ranges of
interatomic distances. This enables its interaction block to update the representations according to the
radial environment of each atom. The sequential updates from three interaction blocks allow SchNet
to construct highly complex many-body representations in the spirit of DTNNs [20] while keeping
rotational invariance due to the radial filters.

4.2 Training with energies and forces

As described above, the interatomic forces are related to the molecular energy, so that we can obtain
an energy-conserving force model by differentiating the energy model w.r.t. the atom positions

∂ Ê
F̂i (Z1 , . . . , Zn , r1 , . . . , rn ) = − (Z1 , . . . , Zn , r1 , . . . , rn ). (4)
∂ri
Chmiela et al. [19] pointed out that this leads to an energy-conserving force-field by construction.
As SchNet yields rotationally invariant energy predictions, the force predictions are rotationally
equivariant by construction. The model has to be at least twice differentiable to allow for gradient
descent of the force loss. We chose a shifted softplus ssp(x) = ln(0.5ex + 0.5) as non-linearity
throughout the network in order to obtain a smooth potential energy surface. The shifting ensures that
ssp(0) = 0 and improves the convergence of the network. This activation function shows similarity
to ELUs [37], while having infinite order of continuity.

5
Table 1: Mean absolute errors for energy predictions in kcal/mol on the QM9 data set with given
training set size N . Best model in bold.
N SchNet DTNN [20] enn-s2s [21] enn-s2s-ens5 [21]
50,000 0.59 0.94 – –
100,000 0.34 0.84 – –
110,462 0.31 – 0.45 0.33

We include the total energy E as well as forces Fi in the training loss to train a neural network that
performs well on both properties:
n
! 2
2 1X ∂ Ê
`(Ê, (E, F1 , . . . , Fn )) = ρkE − Êk + Fi − − . (5)
n i=0 ∂Ri
This kind of loss has been used before for fitting a restricted potential energy surfaces with MLPs [38].
In our experiments, we use ρ = 0.01 for combined energy and force training. The value of ρ was
optimized empirically to account for different scales of energy and forces.
Due to the relation of energies and forces reflected in the model, we expect to see improved gen-
eralization, however, at a computational cost. As we need to perform a full forward and backward
pass on the energy model to obtain the forces, the resulting force model is twice as deep and, hence,
requires about twice the amount of computation time.
Even though the GDML model captures this relationship between energies and forces, it is explicitly
optimized to predict the force field while the energy prediction is a by-product. Models such as
circular fingerprints [17], molecular graph convolutions or message-passing neural networks[21] for
property prediction across chemical compound space are only concerned with equilibrium molecules,
i.e., the special case where the forces are vanishing. They can not be trained with forces in a similar
manner, as they include discontinuities in their predicted potential energy surface caused by discrete
binning or the use of one-hot encoded bond type information.

5 Experiments and results

In this section, we apply the SchNet to three different quantum chemistry datasets: QM9, MD17 and
ISO17. We designed the experiments such that each adds another aspect towards modeling chemical
space. While QM9 only contains equilibrium molecules, for MD17 we predict conformational
changes of molecular dynamics of single molecules. Finally, we present ISO17 combining both
chemical and structural changes.
For all datasets, we report mean absolute errors in kcal/mol for the energies and in kcal/mol/Å for
the forces. The architecture of the network was fixed after an evaluation on the MD17 data sets for
benzene and ethanol (see supplement). In each experiment, we split the data into a training set of
given size N and use a validation set of 1,000 examples for early stopping. The remaining data is
used as test set. All models are trained with SGD using the ADAM optimizer [39] with 32 molecules
per mini-batch. We use an initial learning rate of 10−3 and an exponential learning rate decay with
ratio 0.96 every 100,000 steps. The model used for testing is obtained using an exponential moving
average over weights with decay rate 0.99.

5.1 QM9 – chemical degrees of freedom

QM9 is a widely used benchmark for the prediction of various molecular properties in equilibrium [10,
40, 41]. Therefore, the forces are zero by definition and do not need to be predicted. In this setting,
we train a single model that generalizes across different compositions and sizes.
QM9 consists of ≈130k organic molecules with up to 9 heavy atoms of the types {C, O, N, F}. As the
size of the training set varies across previous work, we trained our models each of these experimental
settings. Table 1 shows the performance of various competing methods for predicting the total energy
(property U0 in QM9). We provide comparisons to the DTNN [20] and the best performing MPNN
configuration denoted enn-s2s and an ensemble of MPNNs (enn-s2s-ens5) [21]. SchNet consistently
obtains state-of-the-art performance with an MAE of 0.31 kcal/mol at 110k training examples.

6
Table 2: Mean absolute errors for energy and force predictions in kcal/mol and kcal/mol/Å, respec-
tively. GDML and SchNet test errors for training with 1,000 and 50,000 examples of molecular
dynamics simulations of small, organic molecules are shown. SchNets were trained only on energies
as well as energies and forces combined. Best results in bold.
N = 1,000 N = 50,000
GDML [19] SchNet DTNN [20] SchNet
forces energy both energy energy both
energy 0.07 1.19 0.08 0.04 0.08 0.07
Benzene
forces 0.23 14.12 0.31 – 1.23 0.17
energy 0.12 2.95 0.12 0.18 0.16 0.09
Toluene
forces 0.24 22.31 0.57 – 1.79 0.09
energy 0.16 2.03 0.13 0.19 0.13 0.08
Malonaldehyde
forces 0.80 20.41 0.66 – 1.51 0.08
energy 0.12 3.27 0.20 0.41 0.25 0.10
Salicylic acid
forces 0.28 23.21 0.85 – 3.72 0.19
energy 0.27 4.20 0.37 – 0.25 0.12
Aspirin
forces 0.99 23.54 1.35 – 7.36 0.33
energy 0.15 0.93 0.08 – 0.07 0.05
Ethanol
forces 0.79 6.56 0.39 – 0.76 0.05
energy 0.11 2.26 0.14 – 0.13 0.10
Uracil
forces 0.24 20.08 0.56 – 3.28 0.11
energy 0.12 3.58 0.16 – 0.20 0.11
Naphtalene
forces 0.23 25.36 0.58 – 2.58 0.11

5.2 MD17 – conformational degrees of freedom

MD17 is a collection of eight molecular dynamics simulations for small organic molecules. These
data sets were introduced by Chmiela et al. [19] for prediction of energy-conserving force fields
using GDML. Each of these consists of a trajectory of a single molecule covering a large variety
of conformations. Here, the task is to predict energies and forces using a separate model for each
trajectory. This molecule-wise training is motivated by the need for highly-accurate force predictions
when doing molecular dynamics.
Table 2 shows the performance of SchNet using 1,000 and 50,000 training examples in comparison
with GDML and DTNN. Using the smaller data set, GDML achieves remarkably accurate energy and
force predictions despite being only trained on forces. The energies are only used to fit the integration
constant. As mentioned before, GDML does not scale well with the number of atoms and training
examples. Therefore, it cannot be trained on 50,000 examples. The DTNN was evaluated only on
four of these MD trajectories using the larger training set [20]. Note that the enn-s2s cannot be used
on this dataset due to discontinuities in its inferred potential energy surface.
We trained SchNet using just energies and using both energies and forces. While the energy-only
model shows high errors for the small training set, the model including forces achieves energy
predictions comparable to GDML. In particular, we observe that SchNet outperforms GDML on the
more flexible molecules malonaldehyde and ethanol, while GDML reaches much lower force errors
on the remaining MD trajectories that all include aromatic rings.
The real strength of SchNet is its scalability, as it outperforms the DTNN in three of four data sets
using 50,000 training examples using only energies in training. Including force information, SchNet
consistently obtains accurate energies and forces with errors below 0.12 kcal/mol and 0.33 kcal/mol/Å,
respectively. Remarkably, when training on energies and forces using 1,000 training examples, SchNet
performs better than training the same model on energies alone for 50,000 examples.

7
 Table 3: Mean absolute errors on C7 O2 H10 isomers in kcal/mol.
mean predictor SchNet
energy energy+forces
known molecules / energy 14.89 0.52 0.36
unknown conformation forces 19.56 4.13 1.00
unknown molecules / energy 15.54 3.11 2.40
unknown conformation forces 19.15 5.71 2.18

5.3 ISO17 – chemical and conformational degrees of freedom

As the next step towards quantum-chemical exploration, we demonstrate the capability of SchNet
to represent a complex potential energy surface including conformational and chemical changes.
We present a new dataset – ISO17 – where we consider short MD trajectories of 129 isomers, i.e.,
chemically different molecules with the same number and types of atoms. In contrast to MD17, we
train a joint model across different molecules. We calculate energies and interatomic forces from short
MD trajectories of 129 molecules drawn randomly from the largest set of isomers in QM9. While
the composition of all included molecules is C7 O2 H10 , the chemical structures are fundamentally
different. With each trajectory consisting of 5,000 conformations, the data set consists of 645,000
labeled examples.
We consider two scenarios with this dataset: In the first variant, the molecular graph structures
present in training are also present in the test data. This demonstrates how well our model is able to
represent a complex potential energy surface with chemical and conformational changes. In the more
challenging scenario, the test data contains a different subset of molecules. Here we evaluate the
generalization of our model to previously unseen chemical structures. We predict forces and energies
in both cases and compare to the mean predictor as a baseline. We draw a subset of 4,000 steps from
80% of the MD trajectories for training and validation. This leaves us with a separate test set for each
scenario: (1) the unseen 1,000 conformations of molecule trajectories included in the training set and
(2) all 5,000 conformations of the remaining 20% of molecules not included in training.
Table 3 shows the performance of the SchNet on both test sets. Our proposed model reaches chemical
accuracy for the prediction of energies and forces for the test set of known molecules. Including
forces in the training improves the performance here as well as on the set of unseen molecules. This
shows that using force information does not only help to accurately predict nearby conformations of
a single molecule, but indeed helps to generalize across chemical compound space.

6 Conclusions

We have proposed continuous-filter convolutional layers as a novel building block for deep neural
networks. In contrast to the usual convolutional layers, these can model unevenly spaced data as
occurring in astronomy, climate reasearch and, in particular, quantum chemistry. We have developed
SchNet to demonstrate the capabilities of continuous-filter convolutional layers in the context of
modeling quantum interactions in molecules. Our architecture respects quantum-chemical constraints
such as rotationally invariant energy predictions as well as rotationally equivariant, energy-conserving
force predictions.
We have evaluated our model in three increasingly challenging experimental settings. Each brings us
one step closer to practical chemical exploration driven by machine learning. SchNet improves the
state-of-the-art in predicting energies for molecules in equilibrium of the QM9 benchmark. Beyond
that, it achieves accurate predictions for energies and forces for all molecular dynamics trajectories in
MD17. Finally, we have introduced ISO17 consisting of 645,000 conformations of various C7 O2 H10
isomers. While we achieve promising results on this new benchmark, modeling chemical and
conformational variations remains difficult and needs further improvement. For this reason, we expect
that ISO17 will become a new standard benchmark for modeling quantum interactions with machine
learning.

8
Acknowledgments
This work was supported by the Federal Ministry of Education and Research (BMBF) for the Berlin
Big Data Center BBDC (01IS14013A). Additional support was provided by the DFG (MU 987/20-1)
and from the European Union’s Horizon 2020 research and innovation program under the Marie
Sklodowska-Curie grant agreement NO 657679. K.R.M. gratefully acknowledges the BK21 program
funded by Korean National Research Foundation grant (No. 2012-005741) and the Institute for
Information & Communications Technology Promotion (IITP) grant funded by the Korea government
(no. 2017-0-00451).

References
[1] M. Rupp, A. Tkatchenko, K.-R. Müller, and O. A. Von Lilienfeld. Fast and accurate modeling
of molecular atomization energies with machine learning. Phys. Rev. Lett., 108(5):058301,
2012.
[2] G. Montavon, M. Rupp, V. Gobre, A. Vazquez-Mayagoitia, K. Hansen, A. Tkatchenko, K.-R.
Müller, and O. A. von Lilienfeld. Machine learning of molecular electronic properties in
chemical compound space. New J. Phys., 15(9):095003, 2013.
[3] K. Hansen, G. Montavon, F. Biegler, S. Fazli, M. Rupp, M. Scheffler, O. A. Von Lilienfeld,
A. Tkatchenko, and K.-R. Müller. Assessment and validation of machine learning methods for
predicting molecular atomization energies. J. Chem. Theory Comput., 9(8):3404–3419, 2013.
[4] K. T. Schütt, H. Glawe, F. Brockherde, A. Sanna, K.-R. Müller, and EKU Gross. How
to represent crystal structures for machine learning: Towards fast prediction of electronic
properties. Phys. Rev. B, 89(20):205118, 2014.
[5] K. Hansen, F. Biegler, R. Ramakrishnan, W. Pronobis, O. A. von Lilienfeld, K.-R. Müller, and
A. Tkatchenko. Machine learning predictions of molecular properties: Accurate many-body
potentials and nonlocality in chemical space. J. Phys. Chem. Lett., 6:2326, 2015.
[6] F. A. Faber, L. Hutchison, B. Huang, Ju. Gilmer, S. S. Schoenholz, G. E. Dahl, O. Vinyals,
S. Kearnes, P. F. Riley, and O. A. von Lilienfeld. Fast machine learning models of electronic
and energetic properties consistently reach approximation errors better than dft accuracy. arXiv
preprint arXiv:1702.05532, 2017.
[7] F. Brockherde, L. Voigt, L. Li, M. E. Tuckerman, K. Burke, and K.-R. Müller. Bypassing the
Kohn-Sham equations with machine learning. Nature Communications, 8(872), 2017.
[8] W. Boomsma and J. Frellsen. Spherical convolutions and their application in molecular mod-
elling. In Advances in Neural Information Processing Systems 30, pages 3436–3446. 2017.
[9] M. Eickenberg, G. Exarchakis, M. Hirn, and S. Mallat. Solid harmonic wavelet scattering:
Predicting quantum molecular energy from invariant descriptors of 3d electronic densities. In
Advances in Neural Information Processing Systems 30, pages 6543–6552. 2017.
[10] R. Ramakrishnan, P. O. Dral, M. Rupp, and O. A. von Lilienfeld. Quantum chemistry structures
and properties of 134 kilo molecules. Scientific Data, 1, 2014.
[11] S. Manzhos and T. Carrington Jr. A random-sampling high dimensional model representation
neural network for building potential energy surfaces. J. Chem. Phys., 125(8):084109, 2006.
[12] R. Malshe, M .and Narulkar, L. M. Raff, M. Hagan, S. Bukkapatnam, P. M. Agrawal, and R. Ko-
manduri. Development of generalized potential-energy surfaces using many-body expansions,
neural networks, and moiety energy approximations. J. Chem. Phys., 130(18):184102, 2009.
[13] J. Behler and M. Parrinello. Generalized neural-network representation of high-dimensional
potential-energy surfaces. Phys. Rev. Lett., 98(14):146401, 2007.
[14] A. P. Bartók, M. C. Payne, R. Kondor, and G. Csányi. Gaussian approximation potentials: The
accuracy of quantum mechanics, without the electrons. Phys. Rev. Lett., 104(13):136403, 2010.

9
[15] J. Behler. Atom-centered symmetry functions for constructing high-dimensional neural network
potentials. J. Chem. Phys., 134(7):074106, 2011.
[16] A. P. Bartók, R. Kondor, and G. Csányi. On representing chemical environments. Phys. Rev. B,
87(18):184115, 2013.
[17] D. K. Duvenaud, D. Maclaurin, J. Iparraguirre, R. Bombarell, T. Hirzel, A. Aspuru-Guzik,
and R. P. Adams. Convolutional networks on graphs for learning molecular fingerprints. In
C. Cortes, N. D. Lawrence, D. D. Lee, M. Sugiyama, and R. Garnett, editors, NIPS, pages
2224–2232, 2015.
[18] S. Kearnes, K. McCloskey, M. Berndl, V. Pande, and P. F. Riley. Molecular graph convolutions:
moving beyond fingerprints. Journal of Computer-Aided Molecular Design, 30(8):595–608,
2016.
[19] S. Chmiela, A. Tkatchenko, H. E. Sauceda, I. Poltavsky, K. T. Schütt, and K.-R. Müller.
Machine learning of accurate energy-conserving molecular force fields. Science Advances, 3(5):
e1603015, 2017.
[20] K. T. Schütt, F. Arbabzadah, S. Chmiela, K.-R. Müller, and A. Tkatchenko. Quantum-chemical
insights from deep tensor neural networks. Nature Communications, 8(13890), 2017.
[21] J. Gilmer, S. S. Schoenholz, P. F. Riley, O. Vinyals, and G. E. Dahl. Neural message passing for
quantum chemistry. In Proceedings of the 34th International Conference on Machine Learning,
pages 1263–1272, 2017.
[22] Y. LeCun, B. Boser, J. S. Denker, D. Henderson, R. E. Howard, W. Hubbard, and L. D. Jackel.
Backpropagation applied to handwritten zip code recognition. Neural computation, 1(4):
541–551, 1989.
[23] A. Krizhevsky, I. Sutskever, and G. E. Hinton. Imagenet classification with deep convolutional
neural networks. In Advances in neural information processing systems, pages 1097–1105,
2012.
[24] A. Karpathy, G. Toderici, S. Shetty, T. Leung, R. Sukthankar, and L. Fei-Fei. Large-scale video
classification with convolutional neural networks. In Proceedings of the IEEE conference on
Computer Vision and Pattern Recognition, pages 1725–1732, 2014.
[25] A. van den Oord, S. Dieleman, H. Zen, K. Simonyan, O. Vinyals, A. Graves, N. Kalchbrenner,
A. Senior, and K. Kavukcuoglu. Wavenet: A generative model for raw audio. In 9th ISCA
Speech Synthesis Workshop, pages 125–125, 2016.
[26] W. Max-Moerbeck, J. L. Richards, T. Hovatta, V. Pavlidou, T. J. Pearson, and A. C. S. Readhead.
A method for the estimation of the significance of cross-correlations in unevenly sampled
red-noise time series. Monthly Notices of the Royal Astronomical Society, 445(1):437–459,
2014.
[27] K. B. Ólafsdóttir, M. Schulz, and M. Mudelsee. Redfit-x: Cross-spectral analysis of unevenly
spaced paleoclimate time series. Computers & Geosciences, 91:11–18, 2016.
[28] L. E. Nieto-Barajas and T. Sinha. Bayesian interpolation of unequally spaced time series.
Stochastic environmental research and risk assessment, 29(2):577–587, 2015.
[29] J. C. Snyder, M. Rupp, K. Hansen, K.-R. Müller, and K. Burke. Finding density functionals
with machine learning. Physical review letters, 108(25):253002, 2012.
[30] M. Hirn, S. Mallat, and N. Poilvert. Wavelet scattering regression of quantum chemical energies.
Multiscale Modeling & Simulation, 15(2):827–863, 2017.
[31] J. Bruna, W. Zaremba, A. Szlam, and Y. Lecun. Spectral networks and locally connected
networks on graphs. In ICLR, 2014.
[32] M. Henaff, J. Bruna, and Y. LeCun. Deep convolutional networks on graph-structured data.
arXiv preprint arXiv:1506.05163, 2015.

10
[33] J. Masci, D. Boscaini, M. Bronstein, and P. Vandergheynst. Geodesic convolutional neural
networks on riemannian manifolds. In Proceedings of the IEEE international conference on
computer vision workshops, pages 37–45, 2015.
[34] X. Jia, B. De Brabandere, T. Tuytelaars, and L. V. Gool. Dynamic filter networks. In D. D. Lee,
M. Sugiyama, U. V. Luxburg, I. Guyon, and R. Garnett, editors, Advances in Neural Information
Processing Systems 29, pages 667–675. 2016.
[35] F. Chollet. Xception: Deep learning with depthwise separable convolutions. arXiv preprint
arXiv:1610.02357, 2016.
[36] K. He, X. Zhang, S. Ren, and J. Sun. Deep residual learning for image recognition. In
Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pages
770–778, 2016.
[37] D.-A. Clevert, T. Unterthiner, and S. Hochreiter. Fast and accurate deep network learning by
exponential linear units (elus). arXiv preprint arXiv:1511.07289, 2015.
[38] A Pukrittayakamee, M Malshe, M Hagan, LM Raff, R Narulkar, S Bukkapatnum, and R Ko-
manduri. Simultaneous fitting of a potential-energy surface and its corresponding force fields
using feedforward neural networks. The Journal of chemical physics, 130(13):134101, 2009.
[39] D. P. Kingma and J. Ba. Adam: A method for stochastic optimization. In ICLR, 2015.
[40] L. C. Blum and J.-L. Reymond. 970 million druglike small molecules for virtual screening in
the chemical universe database GDB-13. J. Am. Chem. Soc., 131:8732, 2009.
[41] J.-L. Reymond. The chemical space project. Acc. Chem. Res., 48(3):722–730, 2015.

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