Docking Studies
Docking and protein structure preparation was performed on Molecular
Operating Environment (MOE 2015.10 and 2016.08) from Chemical Computing
Group, Canada. Protein-Ligand docking was designed such that the ligands
are placed in the site using the Triangle Matcher method, and ranked
with the London ΔG (Wright, Anderson, Shadnia, Durst, &
Katzenellenbogen, 2013) scoring function. The initial poses and score
were then refined for energy minimization in the binding pocket and
rescored using GBVI/WSA ΔG (Corbeil, Williams, & Labute, 2012) scoring
function under the Amber12:EHT forcefield set. The target protein and
ligands were allowed to sample alternative conformations to allow for
induced-fit binding of protein-ligand complex. The highest docking score
conformation was used in molecular dynamics (MD) simulation and a final
binding affinity reported from the ensemble average using GBVI/WSA ΔG
calculation. Accessible solvent area (ASA) was calculated from a single
molecular structure using a lattice and a 0-potential contour of the van
der Waals potential. Using the median of each potential value as the
iso-contour cutoff, the surface was then extended to adjacent grid
triangles to smoothen the patch transition (Jorgensen, Maxwell, &
TiradoRives, 1996; Wildman & Crippen, 1999). Docking scores were
determined for antibody molecules 1, 2, and 3 all IgG1 (mAb1 (pI =
7.59), mAb2 (pI = 7.96), and mAb3 (pI = 8.38)) and protonated at pH 5.5.