Mol-MoE: Training Preference-Guided Routers for Molecule Generation

Recent advances in language models have enabled framing molecule generation as sequence modeling. However, existing approaches often rely on single-objective reinforcement learning, limiting their applicability to real-world drug design, where multiple competing properties must be optimized. Traditional multi-objective reinforcement learning (MORL) methods require costly retraining for each new objective combination, making rapid exploration of trade-offs impractical. To overcome these limitations, we introduce Mol-MoE, a mixture-of-experts (MoE) architecture that enables efficient test-time steering of molecule generation without retraining. Central to our approach is a preference-based router training objective that incentivizes the router to combine experts in a way that aligns with user-specified trade-offs. This provides improved flexibility in exploring the chemical property space at test time, facilitating rapid trade-off exploration. Benchmarking against state-of-the-art methods, we show that Mol-MoE achieves superior sample quality and steerability.

MaestroMotif: Skill Design from Artificial Intelligence Feedback

Describing skills in natural language has the potential to provide an accessible way to inject human knowledge about decision-making into an AI system. We present MaestroMotif, a method for AI-assisted skill design, which yields high-performing and adaptable agents. MaestroMotif leverages the capabilities of Large Language Models (LLMs) to effectively create and reuse skills. It first uses an LLM's feedback to automatically design rewards corresponding to each skill, starting from their natural language description. Then, it employs an LLM's code generation abilities, together with reinforcement learning, for training the skills and combining them to implement complex behaviors specified in language. We evaluate MaestroMotif using a suite of complex tasks in the NetHack Learning Environment (NLE), demonstrating that it surpasses existing approaches in both performance and usability.

Exploring Scaling Trends in LLM Robustness

Language model capabilities predictably improve from scaling a model's size and training data. Motivated by this, increasingly large language models have been trained, yielding an array of impressive capabilities. Yet these models are vulnerable to adversarial prompts, such as "jailbreaks" that hijack models to perform undesired behaviors, posing a significant risk of misuse. Prior work indicates that computer vision models become more robust with model and data scaling, raising the question: does language model robustness also improve with scale? We study this question empirically, finding that larger models respond substantially better to adversarial training, but there is little to no benefit from model scale in the absence of explicit defenses.

Decoupling regularization from the action space

Regularized reinforcement learning (RL), particularly the entropy-regularized kind, has gained traction in optimal control and inverse RL. While standard unregularized RL methods remain unaffected by changes in the number of actions, we show that it can severely impact their regularized counterparts. This paper demonstrates the importance of decoupling the regularizer from the action space: that is, to maintain a consistent level of regularization regardless of how many actions are involved to avoid over-regularization. Whereas the problem can be avoided by introducing a task-specific temperature parameter, it is often undesirable and cannot solve the problem when action spaces are state-dependent. In the state-dependent action context, different states with varying action spaces are regularized inconsistently. We introduce two solutions: a static temperature selection approach and a dynamic counterpart, universally applicable where this problem arises. Implementing these changes improves performance on the DeepMind control suite in static and dynamic temperature regimes and a biological sequence design task.

Generative Active Learning for the Search of Small-molecule Protein Binders

Despite substantial progress in machine learning for scientific discovery in recent years, truly de novo design of small molecules which exhibit a property of interest remains a significant challenge. We introduce LambdaZero, a generative active learning approach to search for synthesizable molecules. Powered by deep reinforcement learning, LambdaZero learns to search over the vast space of molecules to discover candidates with a desired property. We apply LambdaZero with molecular docking to design novel small molecules that inhibit the enzyme soluble Epoxide Hydrolase 2 (sEH), while enforcing constraints on synthesizability and drug-likeliness. LambdaZero provides an exponential speedup in terms of the number of calls to the expensive molecular docking oracle, and LambdaZero de novo designed molecules reach docking scores that would otherwise require the virtual screening of a hundred billion molecules. Importantly, LambdaZero discovers novel scaffolds of synthesizable, drug-like inhibitors for sEH. In in vitro experimental validation, a series of ligands from a generated quinazoline-based scaffold were synthesized, and the lead inhibitor N-(4,6-di(pyrrolidin-1-yl)quinazolin-2-yl)-N-methylbenzamide (UM0152893) displayed sub-micromolar enzyme inhibition of sEH.

Maxwell's Demon at Work: Efficient Pruning by Leveraging Saturation of Neurons

When training deep neural networks, the phenomenon of $\textit{dying neurons}$ $\unicode{x2013}$units that become inactive or saturated, output zero during training$\unicode{x2013}$ has traditionally been viewed as undesirable, linked with optimization challenges, and contributing to plasticity loss in continual learning scenarios. In this paper, we reassess this phenomenon, focusing on sparsity and pruning. By systematically exploring the impact of various hyperparameter configurations on dying neurons, we unveil their potential to facilitate simple yet effective structured pruning algorithms. We introduce $\textit{Demon Pruning}$ (DemP), a method that controls the proliferation of dead neurons, dynamically leading to network sparsity. Achieved through a combination of noise injection on active units and a one-cycled schedule regularization strategy, DemP stands out for its simplicity and broad applicability. Experiments on CIFAR10 and ImageNet datasets demonstrate that DemP surpasses existing structured pruning techniques, showcasing superior accuracy-sparsity tradeoffs and training speedups. These findings suggest a novel perspective on dying neurons as a valuable resource for efficient model compression and optimization.

Do Transformer World Models Give Better Policy Gradients?

A natural approach for reinforcement learning is to predict future rewards by unrolling a neural network world model, and to backpropagate through the resulting computational graph to learn a policy. However, this method often becomes impractical for long horizons since typical world models induce hard-to-optimize loss landscapes. Transformers are known to efficiently propagate gradients over long horizons: could they be the solution to this problem? Surprisingly, we show that commonly-used transformer world models produce circuitous gradient paths, which can be detrimental to long-range policy gradients. To tackle this challenge, we propose a class of world models called Actions World Models (AWMs), designed to provide more direct routes for gradient propagation. We integrate such AWMs into a policy gradient framework that underscores the relationship between network architectures and the policy gradient updates they inherently represent. We demonstrate that AWMs can generate optimization landscapes that are easier to navigate even when compared to those from the simulator itself. This property allows transformer AWMs to produce better policies than competitive baselines in realistic long-horizon tasks.

Bridging State and History Representations: Understanding Self-Predictive RL

Representations are at the core of all deep reinforcement learning (RL) methods for both Markov decision processes (MDPs) and partially observable Markov decision processes (POMDPs). Many representation learning methods and theoretical frameworks have been developed to understand what constitutes an effective representation. However, the relationships between these methods and the shared properties among them remain unclear. In this paper, we show that many of these seemingly distinct methods and frameworks for state and history abstractions are, in fact, based on a common idea of self-predictive abstraction. Furthermore, we provide theoretical insights into the widely adopted objectives and optimization, such as the stop-gradient technique, in learning self-predictive representations. These findings together yield a minimalist algorithm to learn self-predictive representations for states and histories. We validate our theories by applying our algorithm to standard MDPs, MDPs with distractors, and POMDPs with sparse rewards. These findings culminate in a set of practical guidelines for RL practitioners.

Maximum entropy GFlowNets with soft Q-learning

Generative Flow Networks (GFNs) have emerged as a powerful tool for sampling discrete objects from unnormalized distributions, offering a scalable alternative to Markov Chain Monte Carlo (MCMC) methods. While GFNs draw inspiration from maximum entropy reinforcement learning (RL), the connection between the two has largely been unclear and seemingly applicable only in specific cases. This paper addresses the connection by constructing an appropriate reward function, thereby establishing an exact relationship between GFNs and maximum entropy RL. This construction allows us to introduce maximum entropy GFNs, which, in contrast to GFNs with uniform backward policy, achieve the maximum entropy attainable by GFNs without constraints on the state space.

Course Correcting Koopman Representations

Koopman representations aim to learn features of nonlinear dynamical systems (NLDS) which lead to linear dynamics in the latent space. Theoretically, such features can be used to simplify many problems in modeling and control of NLDS. In this work we study autoencoder formulations of this problem, and different ways they can be used to model dynamics, specifically for future state prediction over long horizons. We discover several limitations of predicting future states in the latent space and propose an inference-time mechanism, which we refer to as Periodic Reencoding, for faithfully capturing long term dynamics. We justify this method both analytically and empirically via experiments in low and high dimensional NLDS.