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This challenge is based on two datasets, kindly donated by Barry Stoddard (Fred Hutchinson Cancer Research) and David Baker (U. of Washington), which center on proteins designed with the Rosetta program. One protein has been shown to bind 17-hydroxyprogesterone (17-OHP), and the other binds cholecalciferol (vitamin D3) and its analogue 25-hydroxycholecalciferol (25-D3).
The 17-OHP binding dataset contains two protein-ligand co-crystal structures. In both cases, the ligand is 17-OHP, and it is the designed proteins that differ. The two proteins share 93% sequence identity, and a good number of the sequence differences are in the binding site. The crystal structures, named PL-2016-1-O-1 and PL-2016-1-O-2, are solved at resolutions of 2.5 and 2.0Å respectively. Water-mediated protein-ligand interactions, involving a few conserved water molecules in the active site, are important in binding. Getting the conformations correct for the non-planar ring puckers in the 17-OHP ligand should add a layer of challenge for this dataset. These facts, coupled with the challenge of computing the difference between the affinities of the two proteins for their common ligand, 17-OHP, should make for an enlightening docking and scoring challenge.
The cholecalciferol binding dataset contains three protein-ligand co-crystal structures, each for a different designed protein variant bound to the ligand 25-D3. The three proteins have sequence identities > 90%, with subtle differences in the binding site. The crystal structures, named PL-2016-1-C-1, PL-2016-1-C-2 and PL-2016-1-C-3, have resolutions 1.9, 2.1 and 1.9 Å respectively. The corresponding binding affinities have been measured, and the affinity of the protein in PL-2016-1-C-1 for vitamin D3 is also available, albeit without a corresponding crystal structure. Water-mediated protein-ligand interactions within the active site are important for binding.
Predict the poses of the 17-OHP and 25-D3 ligands with their respective proteins, as well as the affinity or affinity rankings for each dataset, including the affinity/ranking of the protein in PL-2016-1-C-1 with ligands 25-D3 and vitamin D3. Note that this challenge has only one stage.
A) Protein structures with the co-crystalized ligand deleted and all the waters retained. No further preparation of the protein structures was done. B) SDfiles for ligands 17-OHP, D3 and 25-D3.
A) Your predicted poses, in a coordinate system aligned with those provided in the inputs, for the following complexes: PL-2016-1-O-1/17-OHP and PL-2016-1-O-2/17-OHP, PL-2016-1-C-1/25-D3, PL-2016-1-C-2/25-D3, and PL-2016-1-C-3/25-D3. B) Your predicted affinities, scores, or affinity rankings for the protein-ligand pairs in each of the two datasets; i.e., for all of the pose-prediction cases plus the affinity for PL-2016-1-C-2/vitamin D3. Each dataset may be ranked separately.