Challenge details, inputs, and (eventually) results for the SAMPL7 series of challenges

See the SAMPL website for information on the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) series of challenges as a whole. This repository focuses specifically on the SAMPL7 series of challenges.

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• Challenge Overview
• Final information on the TrimerTrip host-guest challenge components in the host_guest/Isaacs_clip directory.
• Final information on the Gibb octa acid-based challenge ("Gibb deep cavity cavitand" (GDCC) challenge) in the host_guest/GDCC_and_guests directory.
• Final information on the cyclodextrin derivatives challenge in the host_guest/cyclodextrin_derivatives directory and in our host-guest challenge description.
• Experimental details for the CD challenge in host_guest_description.md
• Host-guest participation instructions with information on the submission format, etc. Our submission system is also now available. Submission formats are available in the subdirectories for the individual host-guest systems.

All three host-guest components of this challenge are now final and launched, though additional supporting files may be added at a later date. The submission deadline is Oct. 4 for the TrimerTrip host-guest challenge and Nov. 1 for the cyclodextrin derivatives and GDCC challenges, due to timescales for data collection and publication of the experimental data.

• GSK logD challenge information as soon as available
• Results (and inputs for) host-guest reference calculations as conducted by Mobley lab, as soon as available. We are conducting alchemical binding free energy calculations with Yank.

• As usual, we make no warranty as to correctness of protonation states, tautomers, conformations and poses provided in these directories. In some cases the most relevant such states may not be known, or multiple states perhaps should be considered. Please exercise caution and due diligence.
• We make an effort to indicate which files are original source files, and which are derived files, so that participants can refer to the original source files to help resolve any uncertainties. We encourage participants to do so.
• While we make every effort to ensure correctness of the files we provide, it is not uncommon for there to be some errors. Please sign up for our e-mail list, since if any critical bugs are found, we will e-mail out appropriate announcements.

• Release 0.1 (July 22, 2019): Finalizes all three host-guest systems and provides sdf, mol2 and PDB files for all guests. Fixes several critical bugs, including fixing several incorrect cyclodextrin-derivative host structure files, fixing errors in a draft TrimerTrip structure file, fixing the SMILES string for TrimerTrip guest g15, and finalizing TrimerTrip guest list.
• Release 0.1.1 (July 22, 2019, DOI 10.5281/zenodo.3346023): Includes updated README files that should have been in release 0.1.
• Release 0.1.2 (Sept. 16, 2019, DOI 10.5281/zenodo.3432298): Fixes protonation states for three "modified cyclodextrin" hosts which had accidentally been prepared (and drawn in ChemDraw) with charged groups present as neutral -- specifically terminal -NH3 groups were provided as -NH2. This affected MGLab19, 24 and 34. Also includes minor maintenance fixes -- listing final rather than tentative buffer conditions for GDCC case (just removing the "tentative" on the buffer identity, and correcting pH from 11.5 to 11.7); updates submission deadlines; fixes missing coordinates in TrimerTrip g11; fixing breakdown into residues in a couple modified cyclodextrin host PDB/mol2 files.
• Release 0.2 (Sept. 24, 2019, DOI 10.5281/zenodo.3459975): Adds host-guest submission template files and instructions; makes more clear which compounds/cases are optional; makes clear that free energy predictions (and uncertainties) are required; enthalpies optional; adds links to host-guest submission system
• Release 0.3 (Sept. 26, 2019, DOI 10.5281/zenodo.3462865): Corrected likely charges/protonation states for MGLab23 and MGLab24 in overview table and in jpg and PDF files. Updated corresponding coded and noncoded CDX files. Fixed a mixture of UNK and MGO residue names. Eliminates all instances of atom name HQ which should correspond to a carbon (which for some reason was instead named HX in some hosts, likely causing problems for some workflows). This has been mapped to atom name C9. Reconnects missing bonds in the PDB section of several models. See PR 42 for full details. Also removes outdated info in README.md and removes extra guest listed in TrimerTrip submission template.

• Update TrimerTrip deadline to Oct. 4.

The SAMPL7 phase of challenges currently includes host-guest binding on three systems: A pair of Gibb Deep Cavity Cavitands (GDCCs), a new "TrimerTrip" molecule from Lyle Isaacs and his group, and a series of cyclodextrin derivatives from Mike Gilson's group. Each host binds one or more guests, and each system involves a total of 9-20 binding free energy calculations. Additional details are provided below. Note that several hosts and/or guests are optional.

A later phase of SAMPL7 is expected to include logD prediction (hopefully with pKa values provided) for a series of small moleculs in several solvents; data is currently being collected in partnership with GSK.

One host-guest series is based on the Gibb Deep Cavity Cavitands (GDCCs), familiar from SAMPL4-6. However, this challenge we swap one of the hosts; previously, we used octa acid (OA) and tetramethyl octa acid (TEMOA); this challenge revisits OA but also utilizes a variant which changes the location of the carboxylates. Both were developed in the laboratory of Dr. Bruce Gibb (Tulane U), who will provide binding free energies and enthalpies, measured by ITC. In this case the challenge is to predict binding of eight compounds to exo-OA (a new host created and studied by the Gibb group and first disclosed in this challenge), and two of these to OA; the other six have been studied previously in OA and can optionally be submitted. Existing benchmark datasets based on the OA host may be of interest for those preparing to tackle these new complexes: https://github.com/MobleyLab/benchmarksets; this perpetual review paper also provides a good introduction to the sampling and experimental issues which are known to be relevant in these systems. See the README on this challenge for more details.

The Isaacs lab is contributing data on binding of a series of guests to an acyclic cucubituril host, codenamed "TrimerTrip", as detailed in host_guest/Isaacs_clip. Guests include compounds which overlap with the GDCC and cyclodextrin-derivative challenges, with a total of roughly 15 complexes being examined. See the README on this challenge for more details.

The Gilson lab is measuring binding of two guests to ten different hosts, comprising beta-cyclodextrin as well as nine different cyclodextrin derivatives which have a single functional group added at one location around the rim of the cavity. Binding is being characterized via ITC and NMR. The two guest compounds (R-rimantadine and trans-4-methylcyclohexanol) overlap with those used in the TrimerTrip and GDCC challenges. Full details are available. Binding to beta-cyclodextrin can optionally be submitted, but literature values for these compounds are available.

This material here is made available under CC-BY and MIT licenses, as appropriate:

• MIT for all software/code
• CC-BY 4.0 for all other materials