Grant: Alliance Grants

DrugBank is a comprehensive, freely available web resource with information on ~12,000 drugs. It is accessed by 1000s of scientists, students, teachers, pharmacists and consumers each day. It is widely used both as a teaching tool and a drug discovery platform. Most data in DrugBank is textual or "one-dimensional" (1D) with some information appearing as pictures (2D). Very little data in DrugBank is structural (3D). However, most activities in drug discovery, development, design and delivery are now based on a detailed understanding of the 3D structures of drugs, their targets and the drugs bound to their targets. Our goal for this "DrugBank-in-3D" project is to add vast amounts of new 3D structural data to DrugBank. This would create a single, easily accessible, fully searchable, comprehensive resource that would contain detailed 3D structures of: 1) known drugs; 2) known drug targets and 3) the drug-target complexes. Our plan is to use the 1D information in DrugBank and combine it with advanced computer methods such as data mining, machine learning and molecular dynamics. All of these will be used to find, extract or generate 1000s of drug and drug-target 3D structures. Putting this 3D information into a single comprehensive resource like DrugBank will enable the development, discovery and design of drugs with higher binding, lower toxicity, reduced side effects and higher bioavailability. Generating these 3D structures requires powerful computers and skilled individuals who have specific training with software for finding, modeling and predicting 3D molecular structures. We will be using software that employs the latest deep learning methods, such as AlphaFold2, AlphaFold-Multimer and Deep Docking, to help generate these structures. When this project is complete, DrugBank will have the world's largest collection of 3D structures for drugs, their targets and their binding interactions. These 3D structures will be publicly available and will provide a superb resource for scientists to quickly explore drug-target interactions, rapidly perform computational drug discovery and accelerate the development of better, safer and more efficacious drugs - all of which could substantially bolster the Canadian drug industry.