JAMUN: Transferable Molecular Conformational Ensemble Generation with Walk-Jump Sampling

Conformational ensembles of protein structures are immensely important both to understanding protein function, and for drug discovery in novel modalities such as cryptic pockets. Current techniques for sampling ensembles are computationally inefficient, or do not transfer to systems outside their training data. We present walk-Jump Accelerated Molecular ensembles with Universal Noise (JAMUN), a step towards the goal of efficiently sampling the Boltzmann distribution of arbitrary proteins. By extending Walk-Jump Sampling to point clouds, JAMUN enables ensemble generation at orders of magnitude faster rates than traditional molecular dynamics or state-of-the-art ML methods. Further, JAMUN is able to predict the stable basins of small peptides that were not seen during training.

EquiJump: Protein Dynamics Simulation via SO(3)-Equivariant Stochastic Interpolants

Mapping the conformational dynamics of proteins is crucial for elucidating their functional mechanisms. While Molecular Dynamics (MD) simulation enables detailed time evolution of protein motion, its computational toll hinders its use in practice. To address this challenge, multiple deep learning models for reproducing and accelerating MD have been proposed drawing on transport-based generative methods. However, existing work focuses on generation through transport of samples from prior distributions, that can often be distant from the data manifold. The recently proposed framework of stochastic interpolants, instead, enables transport between arbitrary distribution endpoints. Building upon this work, we introduce EquiJump, a transferable SO(3)-equivariant model that bridges all-atom protein dynamics simulation time steps directly. Our approach unifies diverse sampling methods and is benchmarked against existing models on trajectory data of fast folding proteins. EquiJump achieves state-of-the-art results on dynamics simulation with a transferable model on all of the fast folding proteins.

Symphony: Symmetry-Equivariant Point-Centered Spherical Harmonics for Molecule Generation

We present Symphony, an $E(3)$-equivariant autoregressive generative model for 3D molecular geometries that iteratively builds a molecule from molecular fragments. Existing autoregressive models such as G-SchNet and G-SphereNet for molecules utilize rotationally invariant features to respect the 3D symmetries of molecules. In contrast, Symphony uses message-passing with higher-degree $E(3)$-equivariant features. This allows a novel representation of probability distributions via spherical harmonic signals to efficiently model the 3D geometry of molecules. We show that Symphony is able to accurately generate small molecules from the QM9 dataset, outperforming existing autoregressive models and approaching the performance of diffusion models.

Artificial Intelligence for Science in Quantum, Atomistic, and Continuum Systems

Advances in artificial intelligence (AI) are fueling a new paradigm of discoveries in natural sciences. Today, AI has started to advance natural sciences by improving, accelerating, and enabling our understanding of natural phenomena at a wide range of spatial and temporal scales, giving rise to a new area of research known as AI for science (AI4Science). Being an emerging research paradigm, AI4Science is unique in that it is an enormous and highly interdisciplinary area. Thus, a unified and technical treatment of this field is needed yet challenging. This paper aims to provide a technically thorough account of a subarea of AI4Science; namely, AI for quantum, atomistic, and continuum systems. These areas aim at understanding the physical world from the subatomic (wavefunctions and electron density), atomic (molecules, proteins, materials, and interactions), to macro (fluids, climate, and subsurface) scales and form an important subarea of AI4Science. A unique advantage of focusing on these areas is that they largely share a common set of challenges, thereby allowing a unified and foundational treatment. A key common challenge is how to capture physics first principles, especially symmetries, in natural systems by deep learning methods. We provide an in-depth yet intuitive account of techniques to achieve equivariance to symmetry transformations. We also discuss other common technical challenges, including explainability, out-of-distribution generalization, knowledge transfer with foundation and large language models, and uncertainty quantification. To facilitate learning and education, we provide categorized lists of resources that we found to be useful. We strive to be thorough and unified and hope this initial effort may trigger more community interests and efforts to further advance AI4Science.

Privacy-Utility Trade-offs in Neural Networks for Medical Population Graphs: Insights from Differential Privacy and Graph Structure

We initiate an empirical investigation into differentially private graph neural networks on population graphs from the medical domain by examining privacy-utility trade-offs at different privacy levels on both real-world and synthetic datasets and performing auditing through membership inference attacks. Our findings highlight the potential and the challenges of this specific DP application area. Moreover, we find evidence that the underlying graph structure constitutes a potential factor for larger performance gaps by showing a correlation between the degree of graph homophily and the accuracy of the trained model.

Learning Integrable Dynamics with Action-Angle Networks

Machine learning has become increasingly popular for efficiently modelling the dynamics of complex physical systems, demonstrating a capability to learn effective models for dynamics which ignore redundant degrees of freedom. Learned simulators typically predict the evolution of the system in a step-by-step manner with numerical integration techniques. However, such models often suffer from instability over long roll-outs due to the accumulation of both estimation and integration error at each prediction step. Here, we propose an alternative construction for learned physical simulators that are inspired by the concept of action-angle coordinates from classical mechanics for describing integrable systems. We propose Action-Angle Networks, which learn a nonlinear transformation from input coordinates to the action-angle space, where evolution of the system is linear. Unlike traditional learned simulators, Action-Angle Networks do not employ any higher-order numerical integration methods, making them extremely efficient at modelling the dynamics of integrable physical systems.

Node-Level Differentially Private Graph Neural Networks

Graph Neural Networks (GNNs) are a popular technique for modelling graph-structured data that compute node-level representations via aggregation of information from the local neighborhood of each node. However, this aggregation implies increased risk of revealing sensitive information, as a node can participate in the inference for multiple nodes. This implies that standard privacy preserving machine learning techniques, such as differentially private stochastic gradient descent (DP-SGD) - which are designed for situations where each data point participates in the inference for one point only - either do not apply, or lead to inaccurate solutions. In this work, we formally define the problem of learning 1-layer GNNs with node-level privacy, and provide an algorithmic solution with a strong differential privacy guarantee. Even though each node can be involved in the inference for multiple nodes, by employing a careful sensitivity analysis anda non-trivial extension of the privacy-by-amplification technique, our method is able to provide accurate solutions with solid privacy parameters. Empirical evaluation on standard benchmarks demonstrates that our method is indeed able to learn accurate privacy preserving GNNs, while still outperforming standard non-private methods that completely ignore graph information.