Novel deep learning strategy to better predict pharmacological properties of candidate drugs and focus discovery efforts

PROJECT SUMMARY Collaborative Drug Discovery, Inc. (CDD) proposes to continue development of a novel approach based on deep learning neural networks to encode molecules into chemically rich vectors. In Phase 1 we demonstrated that this representation enables computational models that more accurately predict the chemical properties of molecules than state-of-the-art models, yet are also far simpler to build because they do not require any expert decisions or optimization to achieve high performance. In Phase 2 we will exploit this unprecedented simplicity to develop an intuitive software package that will for the first time enable any chemist or biologist working in drug discovery to create and run their own predictive models – without relying on specialized cheminformatics expertise – yet still achieve or exceed the accuracy of the best currently available techniques. Scientists engaged in drug discovery research from academic laboratories to large pharmaceutical companies rely on computational QSAR models to predict pharmacologically relevant properties and obviate the need to perform expensive, time-consuming assays (many of which require animal studies) for every molecule of interest. Improved models will enable researchers to select lead candidate series more effectively, explore chemical space around leads to generate novel IP more efficiently, reduce failure rates for compounds advancing through the drug discovery pipeline, and accelerate the entire drug discovery process. These benefits will be realized broadly across most therapeutic areas.We also plan to take the technology one step further, leveraging our chemically rich vector representation to enable the software to creatively suggest novel compounds (which do not appear in the training libraries, screening libraries, or lead series) that outperform the lead candidates simultaneously on bioactivity, ADME/Tox and PK assays . Solving this inverse problem is the Holy Grail of computational medicinal chemistry and has the potential to revolutionize drug discovery. !PROJECT NARRATIVE The proposed project will create novel computational tools that will help researchers to understand whether potential new drugs are likely to be both safe and effective, and identify similar compounds that are likely to be safer and more effective against the same target. This innovative capability will help to accelerate the discovery and development of novel and improved drugs against a wide range of diseases. !