Use case: FXR #3
Description
=== Attachment ===
Input:
fxr_raw.pdb
Output:
fxr_ready.pdb
fxr_str_wat.pdb
=== Setup description ===
The structure of Farnesoid X Receptor provided by the D3R Grand Challenge organizers was used as initial template. Prior to MD simulations it was necessary to model the fragment comprised between residues Ala459-Lys464 that was not resolved in the crystallographic structure. To this end, protein residues between Asn448 and Gln476 were replaced by the same fragment of the structure with PDBid: 3OKH following backbone superposition of both structures. Subsequently, ACE capping groups were added to residues Met247 of FXR and Asp743 of the co activator fragment and a NME capping group was attached to residue Asp755 of the co activator fragment. Standard protonation states were assumed for all tritratable protein side chains and all histidine residues were modelled in their neutral ε-protonated tautomer. In order to maximize the available space in the binding site, of the multiple occupancies displayed for side chains of residues His298 and Asn297 those that more closely resembled the orientation found in 3OKH were retained and the rotamer of the side chain of Arg335 was manually modified to reduce potential steric clashes with voluminous ligands. Crystallographic positions for water molecules in the original structure were retained to assemble the final complex structure.