Generative Models Should at Least Be Able to Design Molecules That Dock Well: A New Benchmark.

Abstract

Designing compounds with desired properties is a key element of the drug discovery process. However, measuring progress in the field has been challenging due to the lack of realistic retrospective benchmarks, and the large cost of prospective validation. To close this gap, we propose a benchmark based on docking, a widely used computational method for assessing molecule binding to a protein. Concretely, the goal is to generate drug-like molecules that are scored highly by SMINA, a popular docking software. We observe that various graph-based generative models fail to propose molecules with a high docking score when trained using a realistically sized training set. This suggests a limitation of the current incarnation of models for de novo drug design. Finally, we also include simpler tasks in the benchmark based on a simpler scoring function. We release the benchmark as an easy to use package available at https://github.com/cieplinski-tobiasz/smina-docking-benchmark. We hope that our benchmark will serve as a stepping stone toward the goal of automatically generating promising drug candidates.