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CB8 - Overview

Challenge timeframe: Aug 23, 2017 to Jan 19, 2018


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 CB8 component of the challenge follows and is reproduced from the SAMPL6 GitHub site:

Cucurbit[8]uril (CB8) is a slightly larger version of the more commonly studied cucurbit[7]uril host. The CB8 host previously appeared in SAMPL3, as summarized here: doi.org/10.1007/s10822-012-9554-1, and additional information about it may be found in a number of prior publications, including DOI 10.1021/jp2110067, 10.1002/chem.201403405, and 10.1021/ja055013x. For the present SAMPL6 challenge, ITC was used to obtain binding free energies and enthalpies for the following 14 guest molecules to this host. However, not all 14 are being included in the main challenge for reasons discussed below; instead, 11 form the primary challenge, and three are offered as bonus cases.

Note that two of the drugs are salts with tartrate or oxalate counterions, so these ions are in solution during the measurements. However, experimental evaluation by the Isaacs lab indicates negligible binding of these anions to CB8 under the present conditions. Compounds listed with no CAS# or source given were purchased as the free base and made into the HCl salts in the Isaacs lab. It is also worth emphasizing that some of these compounds, particularly quinine, are complex stereochemically. We have endeavored to provide correct starting structures, but would advise checking our work, and keeping an eye on the stereochemistry during all cheminformatics and modeling steps, to avoid inadvertent changes in stereochemistry.

CB8 has a larger binding cavity than CB7, and there is the possibility of 1:1 and/or 1:2 CB[8]:guest binding. This has been assessed experimentally and aricept and cyclohexane diamine were found bind in 1:2 complexes, whereas the other compounds do not. Oxaliplatin is also potentially complex due to the platinum atom it contains. As a consequence, these three compounds are not being included in our main challenge. Accordingly, the main challenge is to compute the 11 binding free energies (or association constants) of the remaining compounds with CB8, and participants are also invited to compute the binding enthalpies. A bonus challenge is to also predict binding affinities for aricept, cyclohexane diamine, and oxaliplatin (highlighted in magenta in the image). All measurements were carried out in aqueous 25 mM sodium phosphate buffer at pH 7.2, at 298 K. Measurements are currently complete for all compounds shown, except Detrol and gallamine triethiodate. You may wish to do these last, just in case unexpected difficulties are encountered for these last two. We will let you know of any updates regarding the experimental work (assuming you either sign up for the SAMPL e-mail list or monitor this GitHub repository).

Previous studies of CB7 have revealed that salt concentration can strongly influence both measured and computed binding free energies; e.g. see review in https://github.com/MobleyLab/benchmarksets, and it seems likely that this will also hold for for CB8.

CB8 - Data Download

Challenge timeframe: Aug 23, 2017 to Jan 19, 2018


Data (08/24/2017 to 01/12/2018)
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CB8 - Protocols

Challenge timeframe: Aug 23, 2017 to Jan 19, 2018


Please join the challenge and .

CB8 - Submissions

Challenge timeframe: Aug 23, 2017 to Jan 19, 2018


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CB8 - Evaluation Results

Challenge timeframe: Aug 23, 2017 to Jan 19, 2018


Evaluation Results

Evaluation results are not available yet.
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