1470-1-0cdid-PosePredictionProtocolSelfDock.txt

Name

SkeleDock

Software

HTMD1.13.8/ACEMD3/Rdkit2018.03.4/mmEnergy

System Preparation Parameters

Assumed pH 5.1
Tautomers considered
Gasteiger charges

System Preparation Method

The system was prepared using HTMD function ProteinPrepare at pH 5.1.
This automatically takes care of the protonation of the protein residues. For the ligands,
manual preparation was done setting charges to each atom with Rdkit. Parameterize,
a tool inside HTMD, took then care of the parameters of the ligands. A total of 2 ns of equilibration
was done, with heavy constraints on the backbone and the sidechains, while the ligand was set free.

Pose Prediction Parameters

Equilibration time 2 ns

Pose Prediction Method

We reuse the poses we predicted in subchallenge 1a. The protocol to generate such poses was
the following: We manually search in PDB for close proteins of the provided fasta sequence,
then we selected, for each of the smiles to dock, the closest cocrystallized ligand among those related
proteins. Finally we use a in-house algorithm (SkeleDock) to search for common dihedrals between the
cocrystallized ligand and the smiles. Those dihedrals which were common were mirrored, so that the conformation
of the molecule to dock match the angle in the cocrystall template. We manually supervised the output until
the result matched our expectations. Once all the poses were ready, we build a different homology model
for each of the docked smiles which had use different PDB codes (most of them were docked into 3K5C).
Next, we equilibrated these systems as explained before. Finally, we selected the frame of the equilibration
which was closer to the initial structure, so that those dihedrals in the ligand which might be in a unfavourable
conformation could relax.
In the current subchallenge, where protein structures are available, we simply align these provide structures
into the proteins we previously submited, efectively substituing the modeled proteins by the provided ones.
Then, we run an automate protocol for energy minimization called mmEnergy, which runs 200 steps of minimization on
the protein-ligand system.

Answer 1

Yes

Answer 2

Yes