The First CACHE Challenge – Testing Diverse Virtual Screening Scoring Methods to Identify Potential LRRK2 Binders

In December 2021, Molecular Forecaster (MFI) applied to participate in the inaugural CACHE Challenge. Organized by the Structural Genomics Consortium (SGC), CACHE (Critical Assessment of Computational Hit-finding Experiments) is a public–private partnership benchmarking initiative to enable the development of computational methods “to compare and improve small-molecule hit-finding algorithms through cycles of prediction and experimental testing.” The MFI team has decided to take multiple research-focused approaches to our predictions in this first CACHE challenge, aiming to learn from our successes and failures. We are putting MFI’s team, expertise, and algorithms to the test, using them as a foundation to push the boundaries beyond our scientific and application successes to-date. We’ve also decided to double-down and share the details of our work with the community. The experimental results are now in and we have conducted a retrospective analysis in the second half of this manuscript.