The recent surge in Generative Artificial Intelligence (AI) has introduced exciting possibilities for computational chemistry. Generative AI methods have made significant progress in sampling molecular structures across chemical species, developing force fields, and speeding up simulations. This Perspective offers a structured overview, beginning with the fundamental theoretical concepts in both Generative AI and computational chemistry. It then covers widely used Generative AI methods, including autoencoders, generative adversarial networks, reinforcement learning, flow models and language models, and highlights their selected applications in diverse areas including force field development, and protein/RNA structure prediction. A key focus is on the challenges these methods face before they become truly predictive, particularly in predicting emergent chemical phenomena. We believe that the ultimate goal of a simulation method or theory is to predict phenomena not seen before, and that Generative AI should be subject to these same standards before it is deemed useful for chemistry. We suggest that to overcome these challenges, future AI models need to integrate core chemical principles, especially from statistical mechanics.

Many computational chemistry and molecular simulation workflows can be expressed as graphs. This abstraction is useful to modularize and potentially reuse existing components, as well as provide parallelization and ease reproducibility. Existing tools represent the computation as a directed acyclic graph (DAG), thus allowing efficient execution by parallelization of concurrent branches. These systems can, however, generally not express cyclic and conditional workflows. We therefore developed Maize, a workflow manager for cyclic and conditional graphs based on the principles of flow-based programming. By running each node of the graph concurrently in separate processes and allowing communication at any time through dedicated inter-node channels, arbitrary graph structures can be executed. We demonstrate the effectiveness of the tool on a dynamic active learning task in computational drug design, involving the use of a small molecule generative model and an associated scoring system.

Theoretical studies on chemical reaction mechanisms have been crucial in organic chemistry. Traditionally, calculating the manually constructed molecular conformations of transition states for chemical reactions using quantum chemical calculations is the most commonly used method. However, this way is heavily dependent on individual experience and chemical intuition. In our previous study, we proposed a research paradigm that uses enhanced sampling in QM/MM molecular dynamics simulations to study chemical reactions. This approach can directly simulate the entire process of a chemical reaction. However, the computational speed limits the use of high-precision potential energy functions for simulations. To address this issue, we present a scheme for training high-precision force fields for molecular modeling using our developed graph-neural-network-based molecular model, molecular configuration transformer. This potential energy function allows for highly accurate simulations at a low computational cost, leading to more precise calculations of the mechanism of chemical reactions. We have used this approach to study a Cope rearrangement reaction and a Carbonyl insertion reaction catalyzed by Manganese. This "AI+Physics" based simulation approach is expected to become a new trend in the theoretical study of organic chemical reaction mechanisms.

Artificial Neural Networks (NN) are already heavily involved in methods and applications for frequent tasks in the field of computational chemistry such as representation of potential energy surfaces (PES) and spectroscopic predictions. This perspective provides an overview of the foundations of neural network-based full-dimensional potential energy surfaces, their architectures, underlying concepts, their representation and applications to chemical systems. Methods for data generation and training procedures for PES construction are discussed and means for error assessment and refinement through transfer learning are presented. A selection of recent results illustrates the latest improvements regarding accuracy of PES representations and system size limitations in dynamics simulations, but also NN application enabling direct prediction of physical results without dynamics simulations. The aim is to provide an overview for the current state-of-the-art NN approaches in computational chemistry and also to point out the current challenges in enhancing reliability and applicability of NN methods on a larger scale.

Quantum computing promises to improve our ability to perform some critical computational tasks in the future. Machine learning is changing the way we use computers in our present everyday life and in science. It is natural to seek connections between these two emerging approaches to computing, in the hope of reaping multiple benefits. The search for connecting links has just started, but we are already seeing a lot of potential in this wild, unexplored territory. We present here two new research articles: "Precise measurement of quantum observables with neural-network estimators," published in Physical Review Research, and "Fermionic neural-network states for ab-initio electronic structure," published in Nature Communications.

While engineering, finance, and commerce have profited immensely from novel algorithms, they are not the only ones. Large-scale computation has been an integral part of the toolkit in the physical sciences for many decades - and some of the recent advances in AI have started to change how scientific discoveries are made. There has been a lot of excitement about prominent achievements in the physical sciences, like using machine learning to render an image of a black hole or the contribution of AlphaFold towards protein folding. This article will cover some of the more prominent usages of AI in chemistry, the parent discipline of the aforementioned protein folding problem. One of the chief goals of chemistry is to understand matter, its properties, and the transformations it can undergo.

The 2022 Conference theme is on exploring the opportunities of machine learning. Chair for the conference is industry expert Darren Green, Director of Molecular Design, GSK. New to 2022 is the AI in Drug Discovery post conference workshops on:"From Drug Discovery to Healthcare, an AI insight" and"Deciphering AI Based Drug Discovery" taking place on 16th March 2022. Interested parties can register for the conference and workshops at and take advantage of the early bird offer to save £400 which expires 30th November 2021. Attend the SMi's 3rd annual AI in Drug Discovery conference and explore the latest industry updates in the selection of targets using AI, decision making within drug discovery and closing the loop on AI in drug discovery.

The last decade has witnessed an experimental revolution in data science and machine learning, epitomised by deep learning methods. Indeed, many high-dimensional learning tasks previously thought to be beyond reach -- such as computer vision, playing Go, or protein folding -- are in fact feasible with appropriate computational scale. Remarkably, the essence of deep learning is built from two simple algorithmic principles: first, the notion of representation or feature learning, whereby adapted, often hierarchical, features capture the appropriate notion of regularity for each task, and second, learning by local gradient-descent type methods, typically implemented as backpropagation. While learning generic functions in high dimensions is a cursed estimation problem, most tasks of interest are not generic, and come with essential pre-defined regularities arising from the underlying low-dimensionality and structure of the physical world. This text is concerned with exposing these regularities through unified geometric principles that can be applied throughout a wide spectrum of applications. Such a 'geometric unification' endeavour, in the spirit of Felix Klein's Erlangen Program, serves a dual purpose: on one hand, it provides a common mathematical framework to study the most successful neural network architectures, such as CNNs, RNNs, GNNs, and Transformers. On the other hand, it gives a constructive procedure to incorporate prior physical knowledge into neural architectures and provide principled way to build future architectures yet to be invented.

Graph neural networks (GNNs) belong to a category of neural networks that operate naturally on data structured as graphs. Despite being what can be a confusing topic, GNNs can be distilled into just a handful of simple concepts. We'll pick a likely familiar starting point: recurrent neural networks. As you may recall, recurrent neural networks are well-suited to data that are arranged in a sequence, such as time series data or language. The defining feature for a recurrent neural network is that the state of an RNN depends not only on the current inputs but also on the network's previous hidden state.

Molecular mechanics (MM) potentials have long been a workhorse of computational chemistry. Leveraging accuracy and speed, these functional forms find use in a wide variety of applications from rapid virtual screening to detailed free energy calculations. Traditionally, MM potentials have relied on human-curated, inflexible, and poorly extensible discrete chemical perception rules (atom types) for applying parameters to molecules or biopolymers, making them difficult to optimize to fit quantum chemical or physical property data. Here, we propose an alternative approach that uses graph nets to perceive chemical environments, producing continuous atom embeddings from which valence and nonbonded parameters can be predicted using a feed-forward neural network. Since all stages are built using smooth functions, the entire process of chemical perception and parameter assignment is differentiable end-to-end with respect to model parameters, allowing new force fields to be easily constructed, extended, and applied to arbitrary molecules. We show that this approach has the capacity to reproduce legacy atom types and can be fit to MM and QM energies and forces, among other targets.