Jamin Chen

Genesis Research Team, Alejandro Dobles, Nina Jovic et al. · cmu

Accurately predicting the three-dimensional structures of protein-ligand complexes remains a fundamental challenge in computational drug discovery that limits the pace and success of therapeutic design. Deep learning methods have recently shown strong potential as structural prediction tools, achieving promising accuracy across diverse biomolecular systems. However, their performance and utility are constrained by scarce experimental data, inefficient architectures, physically invalid poses, and the limited ability to exploit auxiliary information available at inference. To address these issues, we introduce Pearl (Placing Every Atom in the Right Location), a foundation model for protein-ligand cofolding at scale. Pearl addresses these challenges with three key innovations: (1) training recipes that include large-scale synthetic data to overcome data scarcity; (2) architectures that incorporate an SO(3)-equivariant diffusion module to inherently respect 3D rotational symmetries, improving generalization and sample efficiency, and (3) controllable inference, including a generalized multi-chain templating system supporting both protein and non-polymeric components as well as dual unconditional/conditional modes. Pearl establishes a new state-of-the-art performance in protein-ligand cofolding. On the key metric of generating accurate (RMSD < 2 Å) and physically valid poses, Pearl surpasses AlphaFold 3 and other open source baselines on the public Runs N' Poses and PoseBusters benchmarks, delivering 14.5% and 14.2% improvements, respectively, over the next best model. In the pocket-conditional cofolding regime, Pearl delivers $3.6\times$ improvement on a proprietary set of challenging, real-world drug targets at the more rigorous RMSD < 1 Å threshold. Finally, we demonstrate that model performance correlates directly with synthetic dataset size used in training.

Dong-Ho Lee, Rahul Khanna, Bill Yuchen Lin et al.

Successfully training a deep neural network demands a huge corpus of labeled data. However, each label only provides limited information to learn from and collecting the requisite number of labels involves massive human effort. In this work, we introduce LEAN-LIFE, a web-based, Label-Efficient AnnotatioN framework for sequence labeling and classification tasks, with an easy-to-use UI that not only allows an annotator to provide the needed labels for a task, but also enables LearnIng From Explanations for each labeling decision. Such explanations enable us to generate useful additional labeled data from unlabeled instances, bolstering the pool of available training data. On three popular NLP tasks (named entity recognition, relation extraction, sentiment analysis), we find that using this enhanced supervision allows our models to surpass competitive baseline F1 scores by more than 5-10 percentage points, while using 2X times fewer labeled instances. Our framework is the first to utilize this enhanced supervision technique and does so for three important tasks -- thus providing improved annotation recommendations to users and an ability to build datasets of (data, label, explanation) triples instead of the regular (data, label) pair.

Bill Yuchen Lin, Xinyue Chen, Jamin Chen et al.

Commonsense reasoning aims to empower machines with the human ability to make presumptions about ordinary situations in our daily life. In this paper, we propose a textual inference framework for answering commonsense questions, which effectively utilizes external, structured commonsense knowledge graphs to perform explainable inferences. The framework first grounds a question-answer pair from the semantic space to the knowledge-based symbolic space as a schema graph, a related sub-graph of external knowledge graphs. It represents schema graphs with a novel knowledge-aware graph network module named KagNet, and finally scores answers with graph representations. Our model is based on graph convolutional networks and LSTMs, with a hierarchical path-based attention mechanism. The intermediate attention scores make it transparent and interpretable, which thus produce trustworthy inferences. Using ConceptNet as the only external resource for Bert-based models, we achieved state-of-the-art performance on the CommonsenseQA, a large-scale dataset for commonsense reasoning.