Stiefel Flow Matching for Moment-Constrained Structure Elucidation

Molecular structure elucidation is a fundamental step in understanding chemical phenomena, with applications in identifying molecules in natural products, lab syntheses, forensic samples, and the interstellar medium. We consider the task of predicting a molecule's all-atom 3D structure given only its molecular formula and moments of inertia, motivated by the ability of rotational spectroscopy to measure these moments. While existing generative models can conditionally sample 3D structures with approximately correct moments, this soft conditioning fails to leverage the many digits of precision afforded by experimental rotational spectroscopy. To address this, we first show that the space of $n$-atom point clouds with a fixed set of moments of inertia is embedded in the Stiefel manifold $\mathrm{St}(n, 4)$. We then propose Stiefel Flow Matching as a generative model for elucidating 3D structure under exact moment constraints. Additionally, we learn simpler and shorter flows by finding approximate solutions for equivariant optimal transport on the Stiefel manifold. Empirically, enforcing exact moment constraints allows Stiefel Flow Matching to achieve higher success rates and faster sampling than Euclidean diffusion models, even on high-dimensional manifolds corresponding to large molecules in the GEOM dataset.

Agents for self-driving laboratories applied to quantum computing

Fully automated self-driving laboratories are promising to enable high-throughput and large-scale scientific discovery by reducing repetitive labour. However, effective automation requires deep integration of laboratory knowledge, which is often unstructured, multimodal, and difficult to incorporate into current AI systems. This paper introduces the k-agents framework, designed to support experimentalists in organizing laboratory knowledge and automating experiments with agents. Our framework employs large language model-based agents to encapsulate laboratory knowledge including available laboratory operations and methods for analyzing experiment results. To automate experiments, we introduce execution agents that break multi-step experimental procedures into state machines, interact with other agents to execute each step and analyze the experiment results. The analyzed results are then utilized to drive state transitions, enabling closed-loop feedback control. To demonstrate its capabilities, we applied the agents to calibrate and operate a superconducting quantum processor, where they autonomously planned and executed experiments for hours, successfully producing and characterizing entangled quantum states at the level achieved by human scientists. Our knowledge-based agent system opens up new possibilities for managing laboratory knowledge and accelerating scientific discovery.

Quantum Deep Equilibrium Models

The feasibility of variational quantum algorithms, the most popular correspondent of neural networks on noisy, near-term quantum hardware, is highly impacted by the circuit depth of the involved parametrized quantum circuits (PQCs). Higher depth increases expressivity, but also results in a detrimental accumulation of errors. Furthermore, the number of parameters involved in the PQC significantly influences the performance through the necessary number of measurements to evaluate gradients, which scales linearly with the number of parameters. Motivated by this, we look at deep equilibrium models (DEQs), which mimic an infinite-depth, weight-tied network using a fraction of the memory by employing a root solver to find the fixed points of the network. In this work, we present Quantum Deep Equilibrium Models (QDEQs): a training paradigm that learns parameters of a quantum machine learning model given by a PQC using DEQs. To our knowledge, no work has yet explored the application of DEQs to QML models. We apply QDEQs to find the parameters of a quantum circuit in two settings: the first involves classifying MNIST-4 digits with 4 qubits; the second extends it to 10 classes of MNIST, FashionMNIST and CIFAR. We find that QDEQ is not only competitive with comparable existing baseline models, but also achieves higher performance than a network with 5 times more layers. This demonstrates that the QDEQ paradigm can be used to develop significantly more shallow quantum circuits for a given task, something which is essential for the utility of near-term quantum computers. Our code is available at https://github.com/martaskrt/qdeq.

Symmetry From Scratch: Group Equivariance as a Supervised Learning Task

In machine learning datasets with symmetries, the paradigm for backward compatibility with symmetry-breaking has been to relax equivariant architectural constraints, engineering extra weights to differentiate symmetries of interest. However, this process becomes increasingly over-engineered as models are geared towards specific symmetries/asymmetries hardwired of a particular set of equivariant basis functions. In this work, we introduce symmetry-cloning, a method for inducing equivariance in machine learning models. We show that general machine learning architectures (i.e., MLPs) can learn symmetries directly as a supervised learning task from group equivariant architectures and retain/break the learned symmetry for downstream tasks. This simple formulation enables machine learning models with group-agnostic architectures to capture the inductive bias of group-equivariant architectures.

How to do impactful research in artificial intelligence for chemistry and materials science

Machine learning has been pervasively touching many fields of science. Chemistry and materials science are no exception. While machine learning has been making a great impact, it is still not reaching its full potential or maturity. In this perspective, we first outline current applications across a diversity of problems in chemistry. Then, we discuss how machine learning researchers view and approach problems in the field. Finally, we provide our considerations for maximizing impact when researching machine learning for chemistry.

A theory of understanding for artificial intelligence: composability, catalysts, and learning

Understanding is a crucial yet elusive concept in artificial intelligence (AI). This work proposes a framework for analyzing understanding based on the notion of composability. Given any subject (e.g., a person or an AI), we suggest characterizing its understanding of an object in terms of its ability to process (compose) relevant inputs into satisfactory outputs from the perspective of a verifier. This highly universal framework can readily apply to non-human subjects, such as AIs, non-human animals, and institutions. Further, we propose methods for analyzing the inputs that enhance output quality in compositions, which we call catalysts. We show how the structure of a subject can be revealed by analyzing its components that act as catalysts and argue that a subject's learning ability can be regarded as its ability to compose inputs into its inner catalysts. Finally we examine the importance of learning ability for AIs to attain general intelligence. Our analysis indicates that models capable of generating outputs that can function as their own catalysts, such as language models, establish a foundation for potentially overcoming existing limitations in AI understanding.

Efficient Evolutionary Search Over Chemical Space with Large Language Models

Molecular discovery, when formulated as an optimization problem, presents significant computational challenges because optimization objectives can be non-differentiable. Evolutionary Algorithms (EAs), often used to optimize black-box objectives in molecular discovery, traverse chemical space by performing random mutations and crossovers, leading to a large number of expensive objective evaluations. In this work, we ameliorate this shortcoming by incorporating chemistry-aware Large Language Models (LLMs) into EAs. Namely, we redesign crossover and mutation operations in EAs using LLMs trained on large corpora of chemical information. We perform extensive empirical studies on both commercial and open-source models on multiple tasks involving property optimization, molecular rediscovery, and structure-based drug design, demonstrating that the joint usage of LLMs with EAs yields superior performance over all baseline models across single- and multi-objective settings. We demonstrate that our algorithm improves both the quality of the final solution and convergence speed, thereby reducing the number of required objective evaluations. Our code is available at http://github.com/zoom-wang112358/MOLLEO

Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS

The discovery of small molecules with therapeutic potential is a long-standing challenge in chemistry and biology. Researchers have increasingly leveraged novel computational techniques to streamline the drug development process to increase hit rates and reduce the costs associated with bringing a drug to market. To this end, we introduce a quantum-classical generative model that seamlessly integrates the computational power of quantum algorithms trained on a 16-qubit IBM quantum computer with the established reliability of classical methods for designing small molecules. Our hybrid generative model was applied to designing new KRAS inhibitors, a crucial target in cancer therapy. We synthesized 15 promising molecules during our investigation and subjected them to experimental testing to assess their ability to engage with the target. Notably, among these candidates, two molecules, ISM061-018-2 and ISM061-22, each featuring unique scaffolds, stood out by demonstrating effective engagement with KRAS. ISM061-018-2 was identified as a broad-spectrum KRAS inhibitor, exhibiting a binding affinity to KRAS-G12D at $1.4 \mu M$. Concurrently, ISM061-22 exhibited specific mutant selectivity, displaying heightened activity against KRAS G12R and Q61H mutants. To our knowledge, this work shows for the first time the use of a quantum-generative model to yield experimentally confirmed biological hits, showcasing the practical potential of quantum-assisted drug discovery to produce viable therapeutics. Moreover, our findings reveal that the efficacy of distribution learning correlates with the number of qubits utilized, underlining the scalability potential of quantum computing resources. Overall, we anticipate our results to be a stepping stone towards developing more advanced quantum generative models in drug discovery.

A Sober Look at LLMs for Material Discovery: Are They Actually Good for Bayesian Optimization Over Molecules?

Automation is one of the cornerstones of contemporary material discovery. Bayesian optimization (BO) is an essential part of such workflows, enabling scientists to leverage prior domain knowledge into efficient exploration of a large molecular space. While such prior knowledge can take many forms, there has been significant fanfare around the ancillary scientific knowledge encapsulated in large language models (LLMs). However, existing work thus far has only explored LLMs for heuristic materials searches. Indeed, recent work obtains the uncertainty estimate -- an integral part of BO -- from point-estimated, non-Bayesian LLMs. In this work, we study the question of whether LLMs are actually useful to accelerate principled Bayesian optimization in the molecular space. We take a sober, dispassionate stance in answering this question. This is done by carefully (i) viewing LLMs as fixed feature extractors for standard but principled BO surrogate models and by (ii) leveraging parameter-efficient finetuning methods and Bayesian neural networks to obtain the posterior of the LLM surrogate. Our extensive experiments with real-world chemistry problems show that LLMs can be useful for BO over molecules, but only if they have been pretrained or finetuned with domain-specific data.

ORGANA: A Robotic Assistant for Automated Chemistry Experimentation and Characterization

Chemistry experimentation is often resource- and labor-intensive. Despite the many benefits incurred by the integration of advanced and special-purpose lab equipment, many aspects of experimentation are still manually conducted by chemists, for example, polishing an electrode in electrochemistry experiments. Traditional lab automation infrastructure faces challenges when it comes to flexibly adapting to new chemistry experiments. To address this issue, we propose a human-friendly and flexible robotic system, ORGANA, that automates a diverse set of chemistry experiments. It is capable of interacting with chemists in the lab through natural language, using Large Language Models (LLMs). ORGANA keeps scientists informed by providing timely reports that incorporate statistical analyses. Additionally, it actively engages with users when necessary for disambiguation or troubleshooting. ORGANA can reason over user input to derive experiment goals, and plan long sequences of both high-level tasks and low-level robot actions while using feedback from the visual perception of the environment. It also supports scheduling and parallel execution for experiments that require resource allocation and coordination between multiple robots and experiment stations. We show that ORGANA successfully conducts a diverse set of chemistry experiments, including solubility assessment, pH measurement, recrystallization, and electrochemistry experiments. For the latter, we show that ORGANA robustly executes a long-horizon plan, comprising 19 steps executed in parallel, to characterize the electrochemical properties of quinone derivatives, a class of molecules used in rechargeable flow batteries. Our user study indicates that ORGANA significantly improves many aspects of user experience while reducing their physical workload. More details about ORGANA can be found at https://ac-rad.github.io/organa/.