Organic synthesis is one of the key stumbling blocks in medicinal chemistry. A necessary yet unsolved step in planning synthesis is solving the forward problem: Given reactants and reagents, predict the products. Similar to other work, we treat reaction prediction as a machine translation problem between simplified molecular-input line-entry system (SMILES) strings (a text-based representation) of reactants, reagents, and the products. We show that a multihead attention Molecular Transformer model outperforms all algorithms in the literature, achieving a top-1 accuracy above 90 on a common benchmark data set. Molecular Transformer makes predictions by inferring the correlations between the presence and absence of chemical motifs in the reactant, reagent, and product present in the data set. Our model requires no handcrafted rules and accurately predicts subtle chemical transformations. Crucially, our model can accurately estimate its own uncertainty, with an uncertainty score that is 89 accurate in term...
In this work, we present a fully attention-based model adapted from @cite_21 , the Molecular Transformer, that outperforms all previous methods while being completely atom-mapping independent and not requiring to split the input into reactants and reagents. Similar to the work of Nam & Kim @cite_1 and @cite_35 , our current model is trained end-to-end, fully data-driven and is free of chemical knowledge rules.
@cite_35 @cite_21 @cite_1
2798657914 2806351858 2610148085 2789541106
Sequence-to-sequence attention-based models have recently shown very promising results on automatic speech recognition (ASR) tasks, which integrate an acoustic, pronunciation and language model into a single neural network. In these models, the Transformer, a new sequence-to-sequence attention-based model relying entirely on self-attention without using RNNs or convolutions, achieves a new single-model state-of-the-art BLEU on neural machine translation (NMT) tasks. Since the outstanding performance of the Transformer, we extend it to speech and concentrate on it as the basic architecture of sequence-to-sequence attention-based model on Mandarin Chinese ASR tasks. Furthermore, we investigate a comparison between syllable based model and context-independent phoneme (CI-phoneme) based model with the Transformer in Mandarin Chinese. Additionally, a greedy cascading decoder with the Transformer is proposed for mapping CI-phoneme sequences and syllable sequences into word sequences. Experiments on HKUST datasets demonstrate that syllable based model with the Transformer performs better than CI-phoneme based counterpart, and achieves a character error rate (CER) of , which is competitive to the state-of-the-art CER of @math by the joint CTC-attention based encoder-decoder network. eep generative models for graph-structured data offer a new angle on the problem of chemical synthesis: by optimizing differentiable models that directly generate molecular graphs, it is pos-sible to side-step expensive search procedures in the discrete and vast space of chemical structures. We introduce MolGAN, an implicit, likelihood-free generative model for small molecular graphs that circumvents the need for expensive graph matching procedures or node ordering heuris-tics of previous likelihood-based methods. Our method adapts generative adversarial networks (GANs) to operate directly on graph-structured data. We combine our approach with a reinforce-ment learning objective to encourage the genera-tion of molecules with specific desired chemical properties. In experiments on the QM9 chemi-cal database, we demonstrate that our model is capable of generating close to 100 valid com-pounds. MolGAN compares favorably both to recent proposals that use string-based (SMILES) representations of molecules and to a likelihood-based method that directly generates graphs, al-beit being susceptible to mode collapse. This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how this model can execute a range of tasks such as generating analogues to a query structure and generating compounds predicted to be active against a biological target. As a proof of principle, the model is first trained to generate molecules that do not contain sulphur. As a second example, the model is trained to generate analogues to the drug Celecoxib, a technique that could be used for scaffold hopping or library expansion starting from a single molecule. Finally, when tuning the model towards generating compounds predicted to be active against the dopamine receptor type 2, the model generates structures of which more than 95 are predicted to be active, including experimentally confirmed actives that have not been included in either the generative model nor the activity prediction model. Open image in new window Graphical abstract . Relying entirely on an attention mechanism, the Transformer introduced by (2017) achieves state-of-the-art results for machine translation. In contrast to recurrent and convolutional neural networks, it does not explicitly model relative or absolute position information in its structure. Instead, it requires adding representations of absolute positions to its inputs. In this work we present an alternative approach, extending the self-attention mechanism to efficiently consider representations of the relative positions, or distances between sequence elements. On the WMT 2014 English-to-German and English-to-French translation tasks, this approach yields improvements of 1.3 BLEU and 0.3 BLEU over absolute position representations, respectively. Notably, we observe that combining relative and absolute position representations yields no further improvement in translation quality. We describe an efficient implementation of our method and cast it as an instance of relation-aware self-attention mechanisms that can generalize to arbitrary graph-labeled inputs.