122 research outputs found
Curiosity as a Self-Supervised Method to Improve Exploration in De novo Drug Design
In recent years, deep learning has demonstrated promising results in de novo
drug design. However, the proposed techniques still lack an efficient
exploration of the large chemical space. Most of these methods explore a small
fragment of the chemical space of known drugs, if the desired molecules were
not found, the process ends. In this work, we introduce a curiosity-driven
method to force the model to navigate many parts of the chemical space,
therefore, achieving higher desirability and diversity as well. At first, we
train a recurrent neural network-based general molecular generator (G), then we
fine-tune G to maximize curiosity and desirability. We define curiosity as the
Tanimoto similarity between two generated molecules, a first molecule generated
by G, and a second one generated by a copy of G (Gcopy). We only backpropagate
the loss through G while keeping Gcopy unchanged. We benchmarked our approach
against two desirable chemical properties related to drug-likeness and showed
that the discovered chemical space can be significantly expanded, thus,
discovering a higher number of desirable molecules with more diversity and
potentially easier to synthesize. All Code and data used in this paper are
available at https://github.com/amine179/Curiosity-RL-for-Drug-Design
In silico generation of novel, drug-like chemical matter using the LSTM neural network
The exploration of novel chemical spaces is one of the most important tasks
of cheminformatics when supporting the drug discovery process. Properly
designed and trained deep neural networks can provide a viable alternative to
brute-force de novo approaches or various other machine-learning techniques for
generating novel drug-like molecules. In this article we present a method to
generate molecules using a long short-term memory (LSTM) neural network and
provide an analysis of the results, including a virtual screening test. Using
the network one million drug-like molecules were generated in 2 hours. The
molecules are novel, diverse (contain numerous novel chemotypes), have good
physicochemical properties and have good synthetic accessibility, even though
these qualities were not specific constraints. Although novel, their structural
features and functional groups remain closely within the drug-like space
defined by the bioactive molecules from ChEMBL. Virtual screening using the
profile QSAR approach confirms that the potential of these novel molecules to
show bioactivity is comparable to the ChEMBL set from which they were derived.
The molecule generator written in Python used in this study is available on
request.Comment: in this version fixed some reference number
Fr\'echet ChemNet Distance: A metric for generative models for molecules in drug discovery
The new wave of successful generative models in machine learning has
increased the interest in deep learning driven de novo drug design. However,
assessing the performance of such generative models is notoriously difficult.
Metrics that are typically used to assess the performance of such generative
models are the percentage of chemically valid molecules or the similarity to
real molecules in terms of particular descriptors, such as the partition
coefficient (logP) or druglikeness. However, method comparison is difficult
because of the inconsistent use of evaluation metrics, the necessity for
multiple metrics, and the fact that some of these measures can easily be
tricked by simple rule-based systems. We propose a novel distance measure
between two sets of molecules, called Fr\'echet ChemNet distance (FCD), that
can be used as an evaluation metric for generative models. The FCD is similar
to a recently established performance metric for comparing image generation
methods, the Fr\'echet Inception Distance (FID). Whereas the FID uses one of
the hidden layers of InceptionNet, the FCD utilizes the penultimate layer of a
deep neural network called ChemNet, which was trained to predict drug
activities. Thus, the FCD metric takes into account chemically and biologically
relevant information about molecules, and also measures the diversity of the
set via the distribution of generated molecules. The FCD's advantage over
previous metrics is that it can detect if generated molecules are a) diverse
and have similar b) chemical and c) biological properties as real molecules. We
further provide an easy-to-use implementation that only requires the SMILES
representation of the generated molecules as input to calculate the FCD.
Implementations are available at: https://www.github.com/bioinf-jku/FCDComment: Implementations are available at:
https://www.github.com/bioinf-jku/FC
Machine Learning for Cancer Drug Combination
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154605/1/cpt1773_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154605/2/cpt1773.pd
Learning Multimodal Graph-to-Graph Translation for Molecular Optimization
We view molecular optimization as a graph-to-graph translation problem. The
goal is to learn to map from one molecular graph to another with better
properties based on an available corpus of paired molecules. Since molecules
can be optimized in different ways, there are multiple viable translations for
each input graph. A key challenge is therefore to model diverse translation
outputs. Our primary contributions include a junction tree encoder-decoder for
learning diverse graph translations along with a novel adversarial training
method for aligning distributions of molecules. Diverse output distributions in
our model are explicitly realized by low-dimensional latent vectors that
modulate the translation process. We evaluate our model on multiple molecular
optimization tasks and show that our model outperforms previous
state-of-the-art baselines
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