We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy barriers separating the states, these transition paths are unlikely to be sampled with standard Molecular Dynamics (MD) simulation. Traditional methods to augment MD with a bias potential to increase the probability of the transition rely on a dimensionality reduction step based on Collective Variables (CVs). Unfortunately, selecting appropriate CVs requires chemical intuition and traditional methods are therefore not always applicable to larger systems. Additionally, when incorrect CVs are used, the bias potential might not be minimal and bias the system along dimensions irrelevant to the transition. Showing a formal relation between the problem of sampling molecular transition paths, the Schr\"odinger bridge problem and stochastic optimal control with neural network policies, we propose a machine learning method for sampling said transitions. Unlike previous non-machine learning approaches our method, named PIPS, does not depend on CVs. We show that our method successful generates low energy transitions for Alanine Dipeptide as well as the larger Polyproline and Chignolin proteins.

Despite the significant recent progress in deep generative models, the underlying structure of their latent spaces is still poorly understood, thereby making the task of performing semantically meaningful latent traversals an open research challenge. Most prior work has aimed to solve this challenge by modeling latent structures linearly, and finding corresponding linear directions which result in `disentangled' generations. In this work, we instead propose to model latent structures with a learned dynamic potential landscape, thereby performing latent traversals as the flow of samples down the landscape's gradient. Inspired by physics, optimal transport, and neuroscience, these potential landscapes are learned as physically realistic partial differential equations, thereby allowing them to flexibly vary over both space and time. To achieve disentanglement, multiple potentials are learned simultaneously, and are constrained by a classifier to be distinct and semantically self-consistent. Experimentally, we demonstrate that our method achieves both more qualitatively and quantitatively disentangled trajectories than state-of-the-art baselines. Further, we demonstrate that our method can be integrated as a regularization term during training, thereby acting as an inductive bias towards the learning of structured representations, ultimately improving model likelihood on similarly structured data.

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. In this paper, we formulate SBDD as a 3D-conditional generation problem and present DiffSBDD, an SE(3)-equivariant 3D-conditional diffusion model that generates novel ligands conditioned on protein pockets. Comprehensive in silico experiments demonstrate the efficiency and effectiveness of DiffSBDD in generating novel and diverse drug-like ligands with competitive docking scores. We further explore the flexibility of the diffusion framework for a broader range of tasks in drug design campaigns, such as off-the-shelf property optimization and partial molecular design with inpainting.

We propose Geometric Clifford Algebra Networks (GCANs) for modeling dynamical systems. GCANs are based on symmetry group transformations using geometric (Clifford) algebras. We first review the quintessence of modern (plane-based) geometric algebra, which builds on isometries encoded as elements of the $\mathrm{Pin}(p,q,r)$ group. We then propose the concept of group action layers, which linearly combine object transformations using pre-specified group actions. Together with a new activation and normalization scheme, these layers serve as adjustable $\textit{geometric templates}$ that can be refined via gradient descent. Theoretical advantages are strongly reflected in the modeling of three-dimensional rigid body transformations as well as large-scale fluid dynamics simulations, showing significantly improved performance over traditional methods.

Quantum error correction is a critical component for scaling up quantum computing. Given a quantum code, an optimal decoder maps the measured code violations to the most likely error that occurred, but its cost scales exponentially with the system size. Neural network decoders are an appealing solution since they can learn from data an efficient approximation to such a mapping and can automatically adapt to the noise distribution. In this work, we introduce a data efficient neural decoder that exploits the symmetries of the problem. We characterize the symmetries of the optimal decoder for the toric code and propose a novel equivariant architecture that achieves state of the art accuracy compared to previous neural decoders.

The numerical solution of partial differential equations (PDEs) is difficult, having led to a century of research so far. Recently, there have been pushes to build neural--numerical hybrid solvers, which piggy-backs the modern trend towards fully end-to-end learned systems. Most works so far can only generalize over a subset of properties to which a generic solver would be faced, including: resolution, topology, geometry, boundary conditions, domain discretization regularity, dimensionality, etc. In this work, we build a solver, satisfying these properties, where all the components are based on neural message passing, replacing all heuristically designed components in the computation graph with backprop-optimized neural function approximators. We show that neural message passing solvers representationally contain some classical methods, such as finite differences, finite volumes, and WENO schemes. In order to encourage stability in training autoregressive models, we put forward a method that is based on the principle of zero-stability, posing stability as a domain adaptation problem. We validate our method on various fluid-like flow problems, demonstrating fast, stable, and accurate performance across different domain topologies, equation parameters, discretizations, etc., in 1D and 2D.

Partial differential equations (PDEs) see widespread use in sciences and engineering to describe simulation of physical processes as scalar and vector fields interacting and coevolving over time. Due to the computationally expensive nature of their standard solution methods, neural PDE surrogates have become an active research topic to accelerate these simulations. However, current methods do not explicitly take into account the relationship between different fields and their internal components, which are often correlated. Viewing the time evolution of such correlated fields through the lens of multivector fields allows us to overcome these limitations. Multivector fields consist of scalar, vector, as well as higher-order components, such as bivectors and trivectors. Their algebraic properties, such as multiplication, addition and other arithmetic operations can be described by Clifford algebras. To our knowledge, this paper presents the first usage of such multivector representations together with Clifford convolutions and Clifford Fourier transforms in the context of deep learning. The resulting Clifford neural layers are universally applicable and will find direct use in the areas of fluid dynamics, weather forecasting, and the modeling of physical systems in general. We empirically evaluate the benefit of Clifford neural layers by replacing convolution and Fourier operations in common neural PDE surrogates by their Clifford counterparts on 2D Navier-Stokes and weather modeling tasks, as well as 3D Maxwell equations. For similar parameter count, Clifford neural layers consistently improve generalization capabilities of the tested neural PDE surrogates. Source code for our PyTorch implementation is available at https://microsoft.github.io/cliffordlayers/.

This work introduces a diffusion model for molecule generation in 3D that is equivariant to Euclidean transformations. Our E(3) Equivariant Diffusion Model (EDM) learns to denoise a diffusion process with an equivariant network that jointly operates on both continuous (atom coordinates) and categorical features (atom types). In addition, we provide a probabilistic analysis which admits likelihood computation of molecules using our model. Experimentally, the proposed method significantly outperforms previous 3D molecular generative methods regarding the quality of generated samples and efficiency at training time.

Energy-based modeling is a promising approach to unsupervised learning, which yields many downstream applications from a single model. The main difficulty in learning energy-based models with the "contrastive approaches" is the generation of samples from the current energy function at each iteration. Many advances have been made to accomplish this subroutine cheaply. Nevertheless, all such sampling paradigms run MCMC targeting the current model, which requires infinitely long chains to generate samples from the true energy distribution and is problematic in practice. This paper proposes an alternative approach to getting these samples and avoiding crude MCMC sampling from the current model. We accomplish this by viewing the evolution of the modeling distribution as (i) the evolution of the energy function, and (ii) the evolution of the samples from this distribution along some vector field. We subsequently derive this time-dependent vector field such that the particles following this field are approximately distributed as the current density model. Thereby we match the evolution of the particles with the evolution of the energy function prescribed by the learning procedure. Importantly, unlike Monte Carlo sampling, our method targets to match the current distribution in a finite time. Finally, we demonstrate its effectiveness empirically compared to MCMC-based learning methods.

Federated learning describes the distributed training of models across multiple clients while keeping the data private on-device. In this work, we view the server-orchestrated federated learning process as a hierarchical latent variable model where the server provides the parameters of a prior distribution over the client-specific model parameters. We show that with simple Gaussian priors and a hard version of the well known Expectation-Maximization (EM) algorithm, learning in such a model corresponds to FedAvg, the most popular algorithm for the federated learning setting. This perspective on FedAvg unifies several recent works in the field and opens up the possibility for extensions through different choices for the hierarchical model. Based on this view, we further propose a variant of the hierarchical model that employs prior distributions to promote sparsity. By similarly using the hard-EM algorithm for learning, we obtain FedSparse, a procedure that can learn sparse neural networks in the federated learning setting. FedSparse reduces communication costs from client to server and vice-versa, as well as the computational costs for inference with the sparsified network - both of which are of great practical importance in federated learning.