Text-based representations of chemicals and proteins can be thought of as unstructured languages codified by humans to describe domain-specific knowledge. Advances in natural language processing (NLP) methodologies in the processing of spoken languages accelerated the application of NLP to elucidate hidden knowledge in textual representations of these biochemical entities and then use it to construct models to predict molecular properties or to design novel molecules. This review outlines the impact made by these advances on drug discovery and aims to further the dialogue between medicinal chemists and computer scientists.
Background. The Drug Discovery Unit (DDU) of Cancer Research UK (CRUK) is using the software Dotmatics for storage and analysis of scientific data during drug discovery process. Whilst the data include event logs, time stamps, activities, and user information are mostly sitting in the database without fully utilising their potential value. Aims. This dissertation aims at extracting knowledge from event logs data which recorded during drug discovery process, to capture the operational business process of the DDU of Cancer Research UK (CRUK) as it was being executed. It provides the evaluations …
Eindhoven University of Technology（埃因霍温理工大学）；Microsoft Research Cambridge（微软剑桥研究院）；Centre for Living Technologies（生命技术中心）
Artificial intelligence (AI) in the form of deep learning bears promise for drug discovery and chemical biology, $\textit{e.g.}$, to predict protein structure and molecular bioactivity, plan organic synthesis, and design molecules $\textit{de novo}$. While most of the deep learning efforts in drug discovery have focused on ligand-based approaches, structure-based drug discovery has the potential to tackle unsolved challenges, such as affinity prediction for unexplored protein targets, binding-mechanism elucidation, and the rationalization of related chemical kinetic properties. Advances in dee…
GlaxoSmithKline（葛兰素史克）；MIT（麻省理工学院）；University of Oxford（牛津大学）；KTH Stockholm（瑞典皇家理工学院）
In vitro cellular experimentation with genetic interventions, using for example CRISPR technologies, is an essential step in early-stage drug discovery and target validation that serves to assess initial hypotheses about causal associations between biological mechanisms and disease pathologies. With billions of potential hypotheses to test, the experimental design space for in vitro genetic experiments is extremely vast, and the available experimental capacity - even at the largest research institutions in the world - pales in relation to the size of this biological hypothesis space. Machine l…
Department of Computer and Data Sciences, Case Western Reserve University（计算机与数据科学系，凯斯西储大学）；Case Western Reserve University（凯斯西储大学）；Department of Biochemistry, Case Western Reserve University（生物化学系，凯斯西储大学）；Center for RNA Science and Therapeutics, Case Western Reserve University（RNA科学与治疗中心，凯斯西储大学）；Department of Biomedical Engineering, Case Western Reserve University（生物医学工程系，凯斯西储大学）
Texas A&M University（德克萨斯农工大学）；University of Iowa（爱荷华大学）
Properties of molecules are indicative of their functions and thus are useful in many applications. With the advances of deep learning methods, computational approaches for predicting molecular properties are gaining increasing momentum. However, there lacks customized and advanced methods and comprehensive tools for this task currently. Here we develop a suite of comprehensive machine learning methods and tools spanning different computational models, molecular representations, and loss functions for molecular property prediction and drug discovery. Specifically, we represent molecules as bot…
Exploring Drug Safety Through Knowledge Graphs: Protein Kinase Inhibitors as a Case Study
David Jackson Institute of Informatics University of Amsterdam（大卫·杰克逊信息学研究所 阿姆斯特丹大学）；Michael Gertz Institute of Computer Science Heidelberg University（迈克尔·格茨计算机科学研究所海德堡大学）；Jürgen Hesser Data Analysis and Modeling in Medicine Mannheim Institute for Intelligent Systems in Medicine (MIISM) Medical Faculty Mannheim, Heidelberg University（朱尔根·赫瑟医学数据分析与建模 马尔姆研究所（MIISM）海德堡大学医学系）
Exploring Optimal Parameters for Ligand-Based Virtual Screening in Early Drug Discovery
Attention Labs（注意力实验室）；Boston Children’s Hospital and Harvard Medical School（波士顿儿童医院和哈佛医学院）；Florida Institute of Technology（佛罗里达理工学院）；Georgia Institute of Technology（佐治亚理工学院）；Worcester Polytechnic Institute（伍斯特理工学院）
Kinase-targeted drug design is challenging. It requires designing inhibitors that can bind to specific kinases when all kinase catalytic domains share a common folding scaffold that binds ATP. Thus, obtaining the desired selectivity, given the whole human kinome, is a fundamental task during early-stage drug discovery. This begins with deciphering the kinase-ligand characteristics, analyzing the structure-activity relationships, and prioritizing the desired drug molecules across the whole kinome. Currently, there are more than 300 kinases with released PDB structures, which provides a substant…
