Graph Dynamical Networks for Unsupervised Learning of Atomic Scale Dynamics in Materials

Understanding the dynamical processes that govern the performance of functional materials is essential for the design of next generation materials to tackle global energy and environmental challenges. Many of these processes involve the dynamics of individual atoms or small molecules in condensed phases, e.g. lithium ions in electrolytes, water molecules in membranes, molten atoms at interfaces, etc., which are difficult to understand due to the complexity of local environments. In this work, we develop graph dynamical networks, an unsupervised learning approach for understanding atomic scale dynamics in arbitrary phases and environments from molecular dynamics simulations. We show that important dynamical information can be learned for various multi-component amorphous material systems, which is difficult to obtain otherwise. With the large amounts of molecular dynamics data generated everyday in nearly every aspect of materials design, this approach provides a broadly useful, automated tool to understand atomic scale dynamics in material systems.Comment: 25 + 7 pages, 5 + 3 figure

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

Quantitative surface field analysis: learning causal models to predict ligand binding affinity and pose.

We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone. The method is closely related to the QMOD approach, substituting a learned scoring field for a pocket constructed of molecular fragments. The problem of mutual ligand alignment is addressed in a general way, and optimal model parameters and ligand poses are identified through multiple-instance machine learning. We provide algorithmic details along with performance results on sixteen structure-activity data sets covering many pharmaceutically relevant targets. In particular, we show how models initially induced from small data sets can extrapolatively identify potent new ligands with novel underlying scaffolds with very high specificity. Further, we show that combining predictions from QuanSA models with those from physics-based simulation approaches is synergistic. QuanSA predictions yield binding affinities, explicit estimates of ligand strain, associated ligand pose families, and estimates of structural novelty and confidence. The method is applicable for fine-grained lead optimization as well as potent new lead identification