The goal of the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) challenge is to improve the accuracy of current computational models to estimate free energy of binding, deprotonation, distribution and other associated physical properties that are useful for the design of new pharmaceutical products. New experimental datasets of physicochemical properties provide opportunities for prospective evaluation of computational prediction methods. Here, aqueous pK_a and a range of bi-phasic logD values for a variety of pharmaceutical compounds were determined through a streamlined automated process to be utilized in the SAMPL8 physical property challenge. The goal of this paper is to provide an in-depth review of the experimental methods utilized to create a comprehensive data set for the blind prediction challenge. The significance of this work involves the use of high throughput experimentation equipment and instrumentation to produce acid dissociation constants for twenty-three drug molecules, as well as distribution coefficients for eleven of those molecules.

The Drug Design Data Resource aims to test and advance the state of the art in protein-ligand modeling by holding community-wide blinded, prediction challenges. Here, we report on our third major round, Grand Challenge 3 (GC3). Held 2017-2018, GC3 centered on the protein Cathepsin S and the kinases VEGFR2, JAK2, p38-α, TIE2, and ABL1, and included both pose-prediction and affinity-ranking components. GC3 was structured much like the prior challenges GC2015 and GC2. First, Stage 1 tested pose prediction and affinity ranking methods; then all available crystal structures were released, and Stage 2 tested only affinity rankings, now in the context of the available structures. Unique to GC3 was the addition of a Stage 1b self-docking subchallenge, in which the protein coordinates from all of the cocrystal structures used in the cross-docking challenge were released, and participants were asked to predict the pose of CatS ligands using these newly released structures. We provide an overview of the outcomes and discuss insights into trends and best-practices.