We report a method to convert discrete representations of molecules to and from a multidimensional continuous representation. This model allows us to generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds. A deep neural network was trained on hundreds of thousands of existing chemical structures to construct three coupled functions: an encoder, a decoder, and a predictor. The encoder converts the discrete representation of a molecule into a real-valued continuous vector, and the decoder converts these continuous vectors back to discrete molecular representations. The predictor estimates chemical properties from the latent continuous vector representation of the molecule. Continuous representations of molecules allow us to automatically generate novel chemical structures by performing simple operations in the latent space, such as decoding random vectors, perturbing known chemical structures, or interpolating between molecules. Continuous representations also allow the use of powerful gradient-based optimization to efficiently guide the search for optimized functional compounds. We demonstrate our method in the domain of drug-like molecules and also in a set of molecules with fewer that nine heavy atoms.

Automatic Chemical Design is a framework for generating novel molecules with optimized properties.

The continued success of Deep Neural Networks (DNNs) in classification tasks has sparked a trend of accelerating their execution with specialized hardware. While published designs easily give an order of magnitude improvement over general-purpose hardware, few look beyond an initial implementation. This paper presents Minerva, a highly automated co-design approach across the algorithm, architecture, and circuit levels to optimize DNN hardware accelerators. Compared to an established fixed-point accelerator baseline, we show that fine-grained, heterogeneous datatype optimization reduces power by 1.5×; aggressive, inline predication and pruning of small activity values further reduces power by 2.0×; and active hardware fault detection coupled with domain-aware error mitigation eliminates an additional 2.7× through lowering SRAM voltages. Across five datasets, these optimizations provide a collective average of 8.1× power reduction over an accelerator baseline without compromising DNN model accuracy. Minerva enables highly accurate, ultra-low power DNN accelerators (in the range of tens of milliwatts), making it feasible to deploy DNNs in power-constrained IoT and mobile devices.

The field of machine learning for drug discovery is witnessing an explosion of novel methods. These methods are often benchmarked on simple physicochemical properties such as solubility or general druglikeness, which can be readily computed. However, these properties are poor representatives of objective functions in drug design, mainly because they do not depend on the candidate compound's interaction with the target. By contrast, molecular docking is a widely applied method in drug discovery to estimate binding affinities. However, docking studies require a significant amount of domain knowledge to set up correctly, which hampers adoption. Here, we present dockstring, a bundle for meaningful and robust comparison of ML models using docking scores. dockstring consists of three components: (1) an open-source Python package for straightforward computation of docking scores, (2) an extensive dataset of docking scores and poses of more than 260,000 molecules for 58 medically relevant targets, and (3) a set of pharmaceutically relevant benchmark tasks such as virtual screening or de novo design of selective kinase inhibitors. The Python package implements a robust ligand and target preparation protocol that allows nonexperts to obtain meaningful docking scores. Our dataset is the first to include docking poses, as well as the first of its size that is a full matrix, thus facilitating experiments in multiobjective optimization and transfer learning. Overall, our results indicate that docking scores are a more realistic evaluation objective than simple physicochemical properties, yielding benchmark tasks that are more challenging and more closely related to real problems in drug discovery.

An expectation propagation (EP) algorithm is proposed for approximate inference in linear regression models with spike-and-slab priors. This EP method is applied to regression tasks in which the number of training instances is small and the number of dimensions of the feature space is large. The problems analyzed include the reconstruction of genetic networks, the recovery of sparse signals, the prediction of user sentiment from customer-written reviews and the analysis of biscuit dough constituents from NIR spectra. The proposed EP method outperforms in most of these tasks another EP method that ignores correlations in the posterior and a variational Bayes technique for approximate inference. Additionally, the solutions generated by EP are very close to those given by Gibbs sampling, which can be taken as the gold standard but can be much more computationally expensive. In the tasks analyzed, spike-and-slab priors generally outperform other sparsifying priors, such as Laplace, Student’s \(t\) and horseshoe priors. The key to the improved predictions with respect to Laplace and Student’s \(t\) priors is the superior selective shrinkage capacity of the spike-and-slab prior distribution.

In this paper we propose using machine learning to improve the design of deep neural network hardware accelerators. We show how to adapt multi-objective Bayesian optimization to overcome a challenging design problem: optimizing deep neural network hardware accelerators for both accuracy and energy efficiency. DNN accelerators exhibit all aspects of a challenging optimization space: the landscape is rough, evaluating designs is expensive, the objectives compete with each other, and both design spaces (algorithmic and microarchitectural) are unwieldy. With multi-objective Bayesian optimization, the design space exploration is made tractable and the design points found vastly outperform traditional methods across all metrics of interest.