scholarly journals Enabling rapid COVID-19 small molecule drug design through scalable deep learning of generative models

Author(s):  
Sam Ade Jacobs ◽  
Tim Moon ◽  
Kevin McLoughlin ◽  
Derek Jones ◽  
David Hysom ◽  
...  

We improved the quality and reduced the time to produce machine learned models for use in small molecule antiviral design. Our globally asynchronous multi-level parallel training approach strong scales to all of Sierra with up to 97.7% efficiency. We trained a novel, character-based Wasserstein autoencoder that produces a higher quality model trained on 1.613 billion compounds in 23 minutes while the previous state of the art takes a day on 1 million compounds. Reducing training time from a day to minutes shifts the model creation bottleneck from computer job turnaround time to human innovation time. Our implementation achieves 318 PFLOPs for 17.1% of half-precision peak. We will incorporate this model into our molecular design loop enabling the generation of more diverse compounds; searching for novel, candidate antiviral drugs improves and reduces the time to synthesize compounds to be tested in the lab.

2020 ◽  
Author(s):  
Kevin Yang ◽  
Wengong Jin ◽  
Kyle Swanson ◽  
Regina Barzilay ◽  
Tommi S Jaakkola

Generative models in molecular design tend to be richly parameterized, data-hungry neural models, as they must create complex structured objects as outputs. Estimating such models from data may be challenging due to the lack of sufficient training data. In this paper, we propose a surprisingly effective self-training approach for iteratively creating additional molecular targets. We first pre-train the generative model together with a simple property predictor. The property predictor is then used as a likelihood model for filtering candidate structures from the generative model. Additional targets are iteratively produced and used in the course of stochastic EM iterations to maximize the log-likelihood that the candidate structures are accepted. A simple rejection (re-weighting) sampler suffices to draw posterior samples since the generative model is already reasonable after pre-training. We demonstrate significant gains over strong baselines for both unconditional and conditional molecular design. In particular, our approach outperforms the previous state-of-the-art in conditional molecular design by over 10% in absolute gain.


2020 ◽  
Author(s):  
Kevin Yang ◽  
Wengong Jin ◽  
Kyle Swanson ◽  
Regina Barzilay ◽  
Tommi S Jaakkola

Generative models in molecular design tend to be richly parameterized, data-hungry neural models, as they must create complex structured objects as outputs. Estimating such models from data may be challenging due to the lack of sufficient training data. In this paper, we propose a surprisingly effective self-training approach for iteratively creating additional molecular targets. We first pre-train the generative model together with a simple property predictor. The property predictor is then used as a likelihood model for filtering candidate structures from the generative model. Additional targets are iteratively produced and used in the course of stochastic EM iterations to maximize the log-likelihood that the candidate structures are accepted. A simple rejection (re-weighting) sampler suffices to draw posterior samples since the generative model is already reasonable after pre-training. We demonstrate significant gains over strong baselines for both unconditional and conditional molecular design. In particular, our approach outperforms the previous state-of-the-art in conditional molecular design by over 10% in absolute gain.


Author(s):  
Yuki Ichikawa ◽  
Michiaki Hiramatsu ◽  
Yusuke Mita ◽  
Makoto Makishima ◽  
Yotaro Matsumoto ◽  
...  

We found a novel molecular design for improvement in the aqueous solubility of small molecule drugs.


2016 ◽  
Vol 20 (17) ◽  
pp. 1827-1834
Author(s):  
Liqian Gao ◽  
Jun Chen ◽  
Yi Hu ◽  
Hongyan Sun ◽  
Yong Siang Ong ◽  
...  

2019 ◽  
Vol 16 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Hui Zhang ◽  
Yibing Ma ◽  
Youyi Sun ◽  
Jialei Liu ◽  
Yaqing Liu ◽  
...  

In this review, small-molecule donors for application in organic solar cells reported in the last three years are highlighted. Especially, the effect of donor molecular structure on power conversion efficiency of organic solar cells is reported in detail. Furthermore, the mechanism is proposed and discussed for explaining the relationship between structure and power conversion efficiency. These results and discussions draw some rules for rational donor molecular design, which is very important for further improving the power conversion efficiency of organic solar cells based on the small-molecule donor.


2020 ◽  
Vol 7 (1) ◽  
pp. 4-16
Author(s):  
Daria Kotlarek ◽  
Agata Pawlik ◽  
Maria Sagan ◽  
Marta Sowała ◽  
Alina Zawiślak-Architek ◽  
...  

Targeted Protein Degradation (TPD) is an emerging new modality of drug discovery that offers unprecedented therapeutic benefits over traditional protein inhibition. Most importantly, TPD unlocks the untapped pool of the proteome that to date has been considered undruggable. Captor Therapeutics (Captor) is the fourth global, and first European, company that develops small molecule drug candidates based on the principles of targeted protein degradation. Captor is located in Basel, Switzerland and Wroclaw, Poland and exploits the best opportunities of the two sites – experience and non-dilutive European grants, and talent pool, respectively. Through over $38 M of funding, Captor has been active in three areas of TPD: molecular glues, bi-specific degraders and direct degraders, ObteronsTM.


Author(s):  
Mehdi Bahri ◽  
Eimear O’ Sullivan ◽  
Shunwang Gong ◽  
Feng Liu ◽  
Xiaoming Liu ◽  
...  

AbstractStandard registration algorithms need to be independently applied to each surface to register, following careful pre-processing and hand-tuning. Recently, learning-based approaches have emerged that reduce the registration of new scans to running inference with a previously-trained model. The potential benefits are multifold: inference is typically orders of magnitude faster than solving a new instance of a difficult optimization problem, deep learning models can be made robust to noise and corruption, and the trained model may be re-used for other tasks, e.g. through transfer learning. In this paper, we cast the registration task as a surface-to-surface translation problem, and design a model to reliably capture the latent geometric information directly from raw 3D face scans. We introduce Shape-My-Face (SMF), a powerful encoder-decoder architecture based on an improved point cloud encoder, a novel visual attention mechanism, graph convolutional decoders with skip connections, and a specialized mouth model that we smoothly integrate with the mesh convolutions. Compared to the previous state-of-the-art learning algorithms for non-rigid registration of face scans, SMF only requires the raw data to be rigidly aligned (with scaling) with a pre-defined face template. Additionally, our model provides topologically-sound meshes with minimal supervision, offers faster training time, has orders of magnitude fewer trainable parameters, is more robust to noise, and can generalize to previously unseen datasets. We extensively evaluate the quality of our registrations on diverse data. We demonstrate the robustness and generalizability of our model with in-the-wild face scans across different modalities, sensor types, and resolutions. Finally, we show that, by learning to register scans, SMF produces a hybrid linear and non-linear morphable model. Manipulation of the latent space of SMF allows for shape generation, and morphing applications such as expression transfer in-the-wild. We train SMF on a dataset of human faces comprising 9 large-scale databases on commodity hardware.


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