SkeleDock
HTMD1.13.8/ACEMD2/Rdkit2018.03.4
Assumed pH 5.1
Tautomers considered
Gasteiger charges
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 time of 2 ns of equilibration
was done, with heavy constraints on the backbone and the sidechains, while the ligand was set free.
Equilibration time 2 ns
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 an 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 one in the cocrystall template. We iterated 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, using ACEMD2 as the MD engine. 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, but keeping the ligand at the same spot.
Yes
Yes