Graph neural networks are currently leading the performance charts in learning-based molecule property prediction and classification. Computational chemistry has, therefore, become the a prominent testbed for generic graph neural networks, as well as for specialized message passing methods. In this work, we demonstrate that the replacement of the underlying networks with hypernetworks leads to a boost in performance, obtaining state of the art results in various benchmarks. A major difficulty in the application of hypernetworks is their lack of stability. We tackle this by combining the current message and the first message. A recent work has tackled the training instability of hypernetworks in the context of error correcting codes, by replacing the activation function of the message passing network with a low-order Taylor approximation of it. We demonstrate that our generic solution can replace this domain-specific solution.
University of Science and Technology of China（中国科学技术大学）；Tencent America（腾讯美国）
Molecular property prediction (e.g., energy) is an essential problem in chemistry and biology. Unfortunately, many supervised learning methods usually suffer from the problem of scarce labeled molecules in the chemical space, where such property labels are generally obtained by Density Functional Theory (DFT) calculation which is extremely computational costly. An effective solution is to incorporate the unlabeled molecules in a semi-supervised fashion. However, learning semi-supervised representation for large amounts of molecules is challenging, including the joint representation issue of bo…
University of Wisconsin — Madison（威斯康星大学麦迪逊分校）；Argonne National Laboratory（阿贡国家实验室）
Predicting the properties of a molecule from its structure is a challenging task. Recently, deep learning methods have improved the state of the art for this task because of their ability to learn useful features from the given data. By treating molecule structure as graphs, where atoms and bonds are modeled as nodes and edges, graph neural networks (GNNs) have been widely used to predict molecular properties. However, the design and development of GNNs for a given data set rely on labor-intensive design and tuning of the network architectures. Neural architecture search (NAS) is a promising a…
MIMOSA: Multi-constraint Molecule Sampling for Molecule Optimization
Georgia Institute of Technology（佐治亚理工学院）；Analytics Center of Excellence, IQVIA（IQVIA卓越分析中心）；North Carolina State University（北卡罗来纳州立大学）；University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）
Nara Institute of Science and Technology（奈良先端科学技术大学院大学）
Molecule property prediction is a fundamental problem for computer-aided drug discovery and materials science. Quantum-chemical simulations such as density functional theory (DFT) have been widely used for calculating the molecule properties, however, because of the heavy computational cost, it is difficult to search a huge number of potential chemical compounds. Machine learning methods for molecular modeling are attractive alternatives, however, the development of expressive, accurate, and scalable graph neural networks for learning molecular representations is still challenging. In this wor…
South China University of Technology（华南理工大学）；Shanghai Jiao Tong University School of Medicine（上海交通大学医学院）
Elucidating and accurately predicting the druggability and bioactivities of molecules plays a pivotal role in drug design and discovery and remains an open challenge. Recently, graph neural networks (GNN) have made remarkable advancements in graph-based molecular property prediction. However, current graph-based deep learning methods neglect the hierarchical information of molecules and the relationships between feature channels. In this study, we propose a well-designed hierarchical informative graph neural networks framework (termed HiGNN) for predicting molecular property by utilizing a co-…
Molecular property prediction is gaining increasing attention due to its diverse applications. One task of particular interests and importance is to predict quantum chemical properties without 3D equilibrium structures. This is practically favorable since obtaining 3D equilibrium structures requires extremely expensive calculations. In this work, we design a deep graph neural network to predict quantum properties by directly learning from 2D molecular graphs. In addition, we propose a 3D graph neural network to learn from low-cost conformer sets, which can be obtained with open-source tools us…
Standard Federated Learning (FL) techniques are limited to clients with identical network architectures. This restricts potential use-cases like cross-platform training or inter-organizational collaboration when both data privacy and architectural proprietary are required. We propose a new FL framework that accommodates heterogeneous client architecture by adopting a graph hypernetwork for parameter sharing. A property of the graph hyper network is that it can adapt to various computational graphs, thereby allowing meaningful parameter sharing across models. Unlike existing solutions, our fram…
Predicting molecular properties (e.g., atomization energy) is an essential issue in quantum chemistry, which could speed up much research progress, such as drug designing and substance discovery. Traditional studies based on density functional theory (DFT) in physics are proved to be time-consuming for predicting large number of molecules. Recently, the machine learning methods, which consider much rule-based information, have also shown potentials for this issue. However, the complex inherent quantum interactions of molecules are still largely underexplored by existing solutions. In this pape…
Pohang University of Science and Technology (POSTECH)（浦项科技大学）；University of Illinois at Urbana-Champaign (UIUC)（伊利诺伊大学厄巴纳-香槟分校）
Recently, graph neural networks (GNNs) have been successfully applied to predicting molecular properties, which is one of the most classical cheminformatics tasks with various applications. Despite their effectiveness, we empirically observe that training a single GNN model for diverse molecules with distinct structural patterns limits its prediction performance. In this paper, motivated by this observation, we propose TopExpert to leverage topology-specific prediction models (referred to as experts), each of which is responsible for each molecular group sharing similar topological semantics. …
Multi-Level Fusion Graph Neural Network for Molecule Property Prediction
School of Mathematical Sciences, University of Electronic Science and Technology of China（电子科技大学数学科学学院）；College of Management Science, Chengdu University of Technology（成都理工大学管理科学学院）
InversionGNN: A Dual Path Network for Multi-Property Molecular Optimization
The Hong Kong University of Science and Technology (Guangzhou)（香港科技大学（广州））；The Hong Kong University of Science and Technology（香港科技大学）；DAMO Academy, Alibaba Group（阿里巴巴达摩院）；Tencent AI Lab（腾讯AI Lab）；University of Texas, Arlington（德克萨斯大学阿灵顿分校）
Synthetic polymers are versatile and widely used materials. Similar to small organic molecules, a large chemical space of such materials is hypothetically accessible. Computational property prediction and virtual screening can accelerate polymer design by prioritizing candidates expected to have favorable properties. However, in contrast to organic molecules, polymers are often not well-defined single structures but an ensemble of similar molecules, which poses unique challenges to traditional chemical representations and machine learning approaches. Here, we introduce a graph representation o…
DenseGNN: universal and scalable deeper graph neural networks for high-performance property prediction in crystals and molecules
School of Materials Science and Engineering, Shanghai Jiao Tong University（上海交通大学材料科学与工程学院）；Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University（上海交通大学张江高等研究院）；Materials Genome Initiative Center, Shanghai Jiao Tong University（上海交通大学材料基因组计划中心）
DNA encoded libraries (DELs) are used for rapid large-scale screening of small molecules against a protein target. These combinatorial libraries are built through several cycles of chemistry and DNA ligation, producing large sets of DNA-tagged molecules. Training machine learning models on DEL data has been shown to be effective at predicting molecules of interest dissimilar from those in the original DEL. Machine learning chemical property prediction approaches rely on the assumption that the property of interest is linked to a single chemical structure. In the context of DNA-encoded librarie…
Designing accurate deep learning models for molecular property prediction plays an increasingly essential role in drug and material discovery. Recently, due to the scarcity of labeled molecules, self-supervised learning methods for learning generalizable and transferable representations of molecular graphs have attracted lots of attention. In this paper, we argue that there exist two major issues hindering current self-supervised learning methods from obtaining desired performance on molecular property prediction, that is, the ill-defined pre-training tasks and the limited model capacity. To t…
With the goal of designing novel inhibitors for SARS-CoV-1 and SARS-CoV-2, we propose the general molecule optimization framework, Molecular Neural Assay Search (MONAS), consisting of three components: a property predictor which identifies molecules with specific desirable properties, an energy model which approximates the statistical similarity of a given molecule to known training molecules, and a molecule search method. In this work, these components are instantiated with graph neural networks (GNNs), Deep Energy Estimator Networks (DEEN) and Monte Carlo tree search (MCTS), respectively. Th…
Drug discovery aims to find novel compounds with specified chemical property profiles. In terms of generative modeling, the goal is to learn to sample molecules in the intersection of multiple property constraints. This task becomes increasingly challenging when there are many property constraints. We propose to offset this complexity by composing molecules from a vocabulary of substructures that we call molecular rationales. These rationales are identified from molecules as substructures that are likely responsible for each property of interest. We then learn to expand rationales into a full …
STOR-i Centre for Doctoral Training（STOR-i博士培训中心）；Lancaster University（兰卡斯特大学）；University of Cambridge（剑桥大学）
We present FlowMO: an open-source Python library for molecular property prediction with Gaussian Processes. Built upon GPflow and RDKit, FlowMO enables the user to make predictions with well-calibrated uncertainty estimates, an output central to active learning and molecular design applications. Gaussian Processes are particularly attractive for modelling small molecular datasets, a characteristic of many real-world virtual screening campaigns where high-quality experimental data is scarce. Computational experiments across three small datasets demonstrate comparable predictive performance to d…
Rapid discovery of new reactions and molecules in recent years has been facilitated by the advancements in high throughput screening, accessibility to a much more complex chemical design space, and the development of accurate molecular modeling frameworks. A holistic study of the growing chemistry literature is, therefore, required that focuses on understanding the recent trends and extrapolating them into possible future trajectories. To this end, several network theory-based studies have been reported that use a directed graph representation of chemical reactions. Here, we perform a study ba…
Sungkyunkwan University（成均馆大学）；New York University（纽约大学）
Although machine learning has been successfully used to propose novel molecules that satisfy desired properties, it is still challenging to explore a large chemical space efficiently. In this paper, we present a conditional molecular design method that facilitates generating new molecules with desired properties. The proposed model, which simultaneously performs both property prediction and molecule generation, is built as a semi-supervised variational autoencoder trained on a set of existing molecules with only a partial annotation. We generate new molecules with desired properties by samplin…
MIT-IBM Watson AI Lab（MIT-IBM沃森人工智能实验室）；IBM Research（IBM研究院）
Molecular optimization aims to discover novel molecules with desirable properties. Two fundamental challenges are: (i) it is not trivial to generate valid molecules in a controllable way due to hard chemical constraints such as the valency conditions, and (ii) it is often costly to evaluate a property of a novel molecule, and therefore, the number of property evaluations is limited. These challenges are to some extent alleviated by a combination of a variational autoencoder (VAE) and Bayesian optimization (BO). VAE converts a molecule into/from its latent continuous vector, and BO optimizes a …
Effective property prediction methods can help accelerate the search for COVID-19 antivirals either through accurate in-silico screens or by effectively guiding on-going at-scale experimental efforts. However, existing prediction tools have limited ability to accommodate scarce or fragmented training data currently available. In this paper, we introduce a novel approach to learn predictors that can generalize or extrapolate beyond the heterogeneous data. Our method builds on and extends recently proposed invariant risk minimization, adaptively forcing the predictor to avoid nuisance variation.…
We propose a simple auto-encoder framework for molecule generation. The molecular graph is first encoded into a continuous latent representation $z$, which is then decoded back to a molecule. The encoding process is easy, but the decoding process remains challenging. In this work, we introduce a simple two-step decoding process. In a first step, a fully connected neural network uses the latent vector $z$ to produce a molecular formula, for example CO$_2$ (one carbon and two oxygen atoms). In a second step, a graph convolutional neural network uses the same latent vector $z$ to place bonds betw…
Machine learning based methods have shown potential for optimizing existing molecules with more desirable properties, a critical step towards accelerating new chemical discovery. Here we propose QMO, a generic query-based molecule optimization framework that exploits latent embeddings from a molecule autoencoder. QMO improves the desired properties of an input molecule based on efficient queries, guided by a set of molecular property predictions and evaluation metrics. We show that QMO outperforms existing methods in the benchmark tasks of optimizing small organic molecules for drug-likeness a…
Quadrant（象限公司）；Vancouver Prostate Centre, UBC（不列颠哥伦比亚大学温哥华前列腺中心）
Variational autoencoders (VAEs) defined over SMILES string and graph-based representations of molecules promise to improve the optimization of molecular properties, thereby revolutionizing the pharmaceuticals and materials industries. However, these VAEs are hindered by the non-unique nature of SMILES strings and the computational cost of graph convolutions. To efficiently pass messages along all paths through the molecular graph, we encode multiple SMILES strings of a single molecule using a set of stacked recurrent neural networks, pooling hidden representations of each atom between SMILES r…
Recently many efforts have been devoted to applying graph neural networks (GNNs) to molecular property prediction which is a fundamental task for computational drug and material discovery. One of major obstacles to hinder the successful prediction of molecule property by GNNs is the scarcity of labeled data. Though graph contrastive learning (GCL) methods have achieved extraordinary performance with insufficient labeled data, most focused on designing data augmentation schemes for general graphs. However, the fundamental property of a molecule could be altered with the augmentation method (lik…
Molecular structure-property relationships are key to molecular engineering for materials and drug discovery. The rise of deep learning offers a new viable solution to elucidate the structure-property relationships directly from chemical data. Here we show that the performance of graph convolutional networks (GCNs) for the prediction of molecular properties can be improved by incorporating attention and gate mechanisms. The attention mechanism enables a GCN to identify atoms in different environments. The gated skip-connection further improves the GCN by updating feature maps at an appropriate…
Molecular property prediction plays a fundamental role in drug discovery to identify candidate molecules with target properties. However, molecular property prediction is essentially a few-shot problem which makes it hard to use regular machine learning models. In this paper, we propose Property-Aware Relation networks (PAR) to handle this problem. In comparison to existing works, we leverage the fact that both relevant substructures and relationships among molecules change across different molecular properties. We first introduce a property-aware embedding function to transform the generic mo…
Synergistic Benefits of Joint Molecule Generation and Property Prediction
Institute of AI for Health, Helmholtz Zentrum Munchen（人工智能与健康研究所，海德堡中心）；Technical University of Munich（慕尼黑技术大学）；School of Computation, Information and Technology（计算、信息与技术学院）；Faculty of Mathematics, Informatics and Mechanics, University of Warsaw（数学、信息学与力学学院，华沙大学）；Ardigen SA（Ardigen公司）；Eindhoven University of Technology（埃因霍温理工大学）
MultiPUFFIN: A Multimodal Domain-Constrained Foundation Model for Molecular Property Prediction of Small Molecules
Department of Chemical Engineering, Norwegian University of Science and Technology (NTNU)（挪威科学与技术大学化学工程系）；Faculty of Industrial Engineering, KU Leuven（鲁文大学工业工程学院）；University of Surrey（萨里大学）
Graph Sampling-based Meta-Learning for Molecular Property Prediction
Zhejiang University（浙江大学）；ZJU-Hangzhou Global Scientific and Technological Innovation Center（浙江大学杭州国际科创中心）；Alibaba-Zhejiang University Joint Research Institute of Frontier Technologies（阿里巴巴-浙江大学前沿技术联合研究院）
GeLLMO: Generalizing Large Language Models for Multi-property Molecule Optimization
Department of Computer Science and Engineering, The Ohio State University, USA（计算机科学与工程系，俄亥俄州立大学）；Translational Data Analytics Institute, The Ohio State University, USA（转化数据分析研究所，俄亥俄州立大学）；Department of Biomedical Informatics, The Ohio State University, USA（生物医学信息学系，俄亥俄州立大学）；College of Pharmacy, The Ohio State University, USA（药学院，俄亥俄州立大学）
Functional Groups are All you Need for Chemically Interpretable Molecular Property Prediction
BioSystems Engineering and Control Lab（生物系统工程与控制实验室）；Indian Institute of Technology Madras（印度理工学院马德拉斯学院）；Wadhwani School of Data Science and AI（瓦德哈尼数据科学与人工智能学校）；Indian Institute of Technology Madras Zanzibar（印度理工学院马德拉斯扎辛巴尔）
Soft causal learning for generalized molecule property prediction: An environment perspective
University of Science and Technology of China（中国科学技术大学）；Suzhou Institute for Advanced Research, University of Science and Technology of China（中国科学技术大学苏州高等研究院）
Deargen Inc.（迪尔根公司）；College of Computing at SungKyunKwan University（成均馆大学计算学院）；Department of Computer Science at Emory University（埃默里大学计算机科学系）
Generating a novel and optimized molecule with desired chemical properties is an essential part of the drug discovery process. Failure to meet one of the required properties can frequently lead to failure in a clinical test which is costly. In addition, optimizing these multiple properties is a challenging task because the optimization of one property is prone to changing other properties. In this paper, we pose this multi-property optimization problem as a sequence translation process and propose a new optimized molecule generator model based on the Transformer with two constraint networks: p…
Large Language Models for Controllable Multi-property Multi-objective Molecule Optimization
Department of Computer Science and Engineering, The Ohio State University, USA（计算机科学与工程系，俄亥俄州立大学）；Translational Data Analytics Institute, The Ohio State University, USA（转化数据分析研究所，俄亥俄州立大学）；Department of Biomedical Informatics, The Ohio State University, USA（生物医学信息学系，俄亥俄州立大学）；College of Pharmacy, The Ohio State University, USA（药学院，俄亥俄州立大学）
In order to continuously represent molecules, we propose a generative model in the form of a VAE which is operating on the 2D-graph structure of molecules. A side predictor is employed to prune the latent space and help the decoder in generating meaningful adjacency tensor of molecules. Other than the potential applicability in drug design and property prediction, we show the superior performance of this technique in comparison to other similar methods based on the SMILES representation of the molecules with RNN based encoder and decoder.
