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Full SAMPL6 details are available on the SAMPL6 GitHub site, and detailed descriptions of the Octa Acid Host-Guest Challenge are in the SAMPL6 Detailed Host-Guest Description; the information there includes structures of the hosts and guests. A brief overview of the Octa Acid/Gibb Deep Cavity Cavitand component of the challenge follows and is reproduced from the SAMPL6 GitHub site:
The two host molecules, OA and TEMOA, are closely related to each other; the latter simply has four methyl groups in place of four hydrogens around the portal to the non-polar binding pocket. This change modifies the shape of the binding cavity. Host TEMOA is described here: doi:10.1021/ja200633d and host OA is described here doi:10.1007/s10822-013-9690-2. These will be very familiar to recent SAMPL participants, as they have formed the basis of other SAMPL challenges. There are also a number of papers from SAMPL4 and SAMPL5 which discuss calculations for this system, as summarized here: doi:10.1007/s10822-014-9735-1 and DOI 10.1007/s10822-016-9974-4. The previous SAMPL5 challenge used the same two hosts but with a different set of guests.
For the present SAMPL6 challenge, experimental binding data are being measured for the association of the following set of eight guest molecules (Figure below) to both OA and TEMOA. Some of these compounds have a chiral center; of these, 2-methyl-4-pentenoic acid was measured as a racemic mixture; the other two were enantiopure. However, because the hosts are both achiral, the handedness of the guests should not affect their affinities. Thus, valid calculations may be carried out with either form. The choice should not affecting the computational results or the validity of the comparison with experiment. However, we have endeavored to provide the correct enantiomer here except for 2-methyl-4-pentenoic acid where one was picked at random.
As of this writing, isothermal titration calorimetry (ITC) measurements have been completed for all guests except 2,2-dimethyl-4-pentenoic acid and the perillic acid. You may wish to start with the other guests, just in case difficulties are encountered with these two. If this happens, we plan to substitute other guest molecules. In all cases, confirmation of the formation of the different 1:1 complexes will be carried out using 1H NMR. The thermodynamic parameters (Ka, ?G?, ?H? and –T?S?) for guest binding will be measured by ITC. If this proves problematic in any cases, 1H NMR titrations will be used instead to determine the Ka values for guest association.
The main challenge for this series is to compute the 16 binding free energies (or association constants), and participants are also invited to compute the binding enthalpies. All measurements are being carried out in aqueous 10 mM sodium phosphate buffer at pH 11.7 ± 0.1, at 298 K. A review of some of the known challenges in predicting binding to OA/TEMOA is provided at http://github.com/mobleylab/benchmarksets and may be useful.