Abstract
Computational tools for structure-based drug design (SBDD) are widely used in drug discovery and can provide valuable insights to advance projects in an efficient and cost-effective manner. However, despite the importance of SBDD to the field, the underlying methodologies and techniques have many limitations. In particular, binding pose and activity predictions (P-AP) are still not consistently reliable. We strongly believe that a limiting factor is the lack of a widely accepted and established community benchmarking process that independently assesses the performance and drives the development of methods, similar to the CASP benchmarking challenge for protein structure prediction. Here, we provide an overview of P-AP, unblinded benchmarking data sets, and blinded benchmarking initiatives (concluded and ongoing) and offer a perspective on learnings and the future of the field. To accelerate a breakthrough on the development of novel P-AP methods, it is necessary for the community to establish and support a long-term benchmark challenge that provides nonbiased training/test/validation sets, a systematic independent validation, and a forum for scientific discussions.