The thermodynamics of guest complexation to octa-acid and tetra-endo-methyl octa-acid: reference data for the sixth statistical assessment of modeling of proteins and ligands (SAMPL6)

Although computer-aided drug design has greatly improved over time, its application in the pharmaceutical industry is still limited by the accuracy of association constant (K_a) predictions. Towards improving this situation, the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) is a series of community-wide blind challenges aimed to advance computational techniques as standard predictive tools in rational drug design (https://en.wikipedia.org/wiki/SAMPL_Challenge). As an empirical contribution to SAMPL6, we report here the K_a and thermodynamic parameters (∆G, ∆H, – T∆S) of eight guests binding to two hosts (OA and TEMOA) using ITC. Both hosts contain a unique, well-defined binding pocket capable of storing guests with up to ten non-hydrogen atoms, whilst the selection of amphiphilic guests contain a range of saturated and unsaturated substituents . The thermodynamic data from this study will allow the challenge participants of SAMPL6 to test the accuracy of their computational protocols for calculating host-guest affinities.