AMARO: All Heavy-Atom Transferable Neural Network Potentials of Protein Thermodynamics

All-atom molecular simulations offer detailed insights into macromolecular phenomena, but their substantial computational cost hinders the exploration of complex biological processes. We introduce Advanced Machine-learning Atomic Representation Omni-force-field (AMARO), a new neural network potential (NNP) that combines an O(3)-equivariant message-passing neural network architecture, TensorNet, with a coarse-graining map that excludes hydrogen atoms. AMARO demonstrates the feasibility of training coarser NNP, without prior energy terms, to run stable protein dynamics with scalability and generalization capabilities.

PlayMolecule pKAce: Small Molecule Protonation through Equivariant Neural Networks

Small molecule protonation is an important part of the preparation of small molecules for many types of computational chemistry protocols. For this, a correct estimation of the pKa values of the protonation sites of molecules is required. In this work, we present pKAce, a new web application for the prediction of micro-pKa values of the molecules' protonation sites. We adapt the state-of-the-art, equivariant, TensorNet model originally developed for quantum mechanics energy and force predictions to the prediction of micro-pKa values. We show that an adapted version of this model can achieve state-of-the-art performance comparable with established models while trained on just a fraction of their training data.

BricksRL: A Platform for Democratizing Robotics and Reinforcement Learning Research and Education with LEGO

We present BricksRL, a platform designed to democratize access to robotics for reinforcement learning research and education. BricksRL facilitates the creation, design, and training of custom LEGO robots in the real world by interfacing them with the TorchRL library for reinforcement learning agents. The integration of TorchRL with the LEGO hubs, via Bluetooth bidirectional communication, enables state-of-the-art reinforcement learning training on GPUs for a wide variety of LEGO builds. This offers a flexible and cost-efficient approach for scaling and also provides a robust infrastructure for robot-environment-algorithm communication. We present various experiments across tasks and robot configurations, providing built plans and training results. Furthermore, we demonstrate that inexpensive LEGO robots can be trained end-to-end in the real world to achieve simple tasks, with training times typically under 120 minutes on a normal laptop. Moreover, we show how users can extend the capabilities, exemplified by the successful integration of non-LEGO sensors. By enhancing accessibility to both robotics and reinforcement learning, BricksRL establishes a strong foundation for democratized robotic learning in research and educational settings.

ACEGEN: Reinforcement learning of generative chemical agents for drug discovery

In recent years, reinforcement learning (RL) has emerged as a valuable tool in drug design, offering the potential to propose and optimize molecules with desired properties. However, striking a balance between capability, flexibility, and reliability remains challenging due to the complexity of advanced RL algorithms and the significant reliance on specialized code. In this work, we introduce ACEGEN, a comprehensive and streamlined toolkit tailored for generative drug design, built using TorchRL, a modern decision-making library that offers efficient and thoroughly tested reusable components. ACEGEN provides a robust, flexible, and efficient platform for molecular design. We validate its effectiveness by benchmarking it across various algorithms and conducting multiple drug discovery case studies. ACEGEN is accessible at https://github.com/acellera/acegen-open.

On the Inclusion of Charge and Spin States in Cartesian Tensor Neural Network Potentials

In this letter, we present an extension to TensorNet, a state-of-the-art equivariant Cartesian tensor neural network potential, allowing it to handle charged molecules and spin states without architectural changes or increased costs. By incorporating these attributes, we address input degeneracy issues, enhancing the model's predictive accuracy across diverse chemical systems. This advancement significantly broadens TensorNet's applicability, maintaining its efficiency and accuracy.

TorchMD-Net 2.0: Fast Neural Network Potentials for Molecular Simulations

Achieving a balance between computational speed, prediction accuracy, and universal applicability in molecular simulations has been a persistent challenge. This paper presents substantial advancements in the TorchMD-Net software, a pivotal step forward in the shift from conventional force fields to neural network-based potentials. The evolution of TorchMD-Net into a more comprehensive and versatile framework is highlighted, incorporating cutting-edge architectures such as TensorNet. This transformation is achieved through a modular design approach, encouraging customized applications within the scientific community. The most notable enhancement is a significant improvement in computational efficiency, achieving a very remarkable acceleration in the computation of energy and forces for TensorNet models, with performance gains ranging from 2-fold to 10-fold over previous iterations. Other enhancements include highly optimized neighbor search algorithms that support periodic boundary conditions and the smooth integration with existing molecular dynamics frameworks. Additionally, the updated version introduces the capability to integrate physical priors, further enriching its application spectrum and utility in research. The software is available at https://github.com/torchmd/torchmd-net.

Navigating protein landscapes with a machine-learned transferable coarse-grained model

The most popular and universally predictive protein simulation models employ all-atom molecular dynamics (MD), but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model with similar prediction performance has been a long-standing challenge. By combining recent deep learning methods with a large and diverse training set of all-atom protein simulations, we here develop a bottom-up CG force field with chemical transferability, which can be used for extrapolative molecular dynamics on new sequences not used during model parametrization. We demonstrate that the model successfully predicts folded structures, intermediates, metastable folded and unfolded basins, and the fluctuations of intrinsically disordered proteins while it is several orders of magnitude faster than an all-atom model. This showcases the feasibility of a universal and computationally efficient machine-learned CG model for proteins.

OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUDA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features on simulations of cyclin-dependent kinase 8 (CDK8) and the green fluorescent protein (GFP) chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations at only a modest increase in cost.

Machine Learning Small Molecule Properties in Drug Discovery

Machine learning (ML) is a promising approach for predicting small molecule properties in drug discovery. Here, we provide a comprehensive overview of various ML methods introduced for this purpose in recent years. We review a wide range of properties, including binding affinities, solubility, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity). We discuss existing popular datasets and molecular descriptors and embeddings, such as chemical fingerprints and graph-based neural networks. We highlight also challenges of predicting and optimizing multiple properties during hit-to-lead and lead optimization stages of drug discovery and explore briefly possible multi-objective optimization techniques that can be used to balance diverse properties while optimizing lead candidates. Finally, techniques to provide an understanding of model predictions, especially for critical decision-making in drug discovery are assessed. Overall, this review provides insights into the landscape of ML models for small molecule property predictions in drug discovery. So far, there are multiple diverse approaches, but their performances are often comparable. Neural networks, while more flexible, do not always outperform simpler models. This shows that the availability of high-quality training data remains crucial for training accurate models and there is a need for standardized benchmarks, additional performance metrics, and best practices to enable richer comparisons between the different techniques and models that can shed a better light on the differences between the many techniques.

TorchRL: A data-driven decision-making library for PyTorch

Striking a balance between integration and modularity is crucial for a machine learning library to be versatile and user-friendly, especially in handling decision and control tasks that involve large development teams and complex, real-world data, and environments. To address this issue, we propose TorchRL, a generalistic control library for PyTorch that provides well-integrated, yet standalone components. With a versatile and robust primitive design, TorchRL facilitates streamlined algorithm development across the many branches of Reinforcement Learning (RL) and control. We introduce a new PyTorch primitive, TensorDict, as a flexible data carrier that empowers the integration of the library's components while preserving their modularity. Hence replay buffers, datasets, distributed data collectors, environments, transforms and objectives can be effortlessly used in isolation or combined. We provide a detailed description of the building blocks, supporting code examples and an extensive overview of the library across domains and tasks. Finally, we show comparative benchmarks to demonstrate its computational efficiency. TorchRL fosters long-term support and is publicly available on GitHub for greater reproducibility and collaboration within the research community. The code is opensourced on https://github.com/pytorch/rl.