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Anchored Design of Protein-Protein Interfaces

Figure 6. IRMSD versus score plots. This figure shows score versus IRMSD plots for each of the 16 structures. RMSD was calculated between the
relaxed crystal structure (input) and AnchoredDesign’s output. Plots are labeled with their PDB ID in the lower right of each cell. Black points are
predictions, red points are relaxed native trajectories, and blue points are conservative relaxed native trajectories which skipped the centroid phase
(see main text). Blue points may lie under red points, and red points may lie under black points. Some high-score points are out of view on all plots;
all low-score points are present. On the RMSD (X) axis, the first, second, and third tic marks represent 1, 2.5, and 5 A˚ ngstroms. Some plots are zoomed
in beyond 5 or 2.5 A˚ ngstroms and fewer tics appear.
doi:10.1371/journal.pone.0020872.g006

lowest scoring. This is probably related to the fact that these loops Examination of this structure (Figure 5, panel 2i25) shows that the
are longer than most loops in this benchmark (see Table 2, interface and the loop are nearly the same set of residues: the
Discussion). AnchoredDesign’s assignment of varied incorrect CDR3 loop of the antibody. The relatively elongated antibody
loops as isoenergetic is probably due to the lack of nearby steric fold and the presence of a C-terminal tail pointing away from the
restraints. The 1qni loop is mostly solvent-exposed, meaning that interface amplify tiny errors in loop structure between the interface
many solutions are possible. The 2hp2 loop borders a ligand and antibody core to produce a relatively large displacement of the
absent during the modeling, freeing volume which then allows for opposite side of the antibody. The prediction shows clearly that
many solutions. AnchoredDesign is correct despite the slightly high LRMSD.

Rigid body placement errors Comparison of loop closure methods
Table 3 shows that the three metrics are slightly inconsistent for To test whether CCD or KIC loop closure was more

structure 2i25, a shark antibody bound to lysozyme.[44] appropriate for AnchoredDesign, all experiments were repeated
Specifically, the loop RMSD and IRMSD metrics indicate a using only CCD or KIC loop remodeling. Three general trends
correct solution, while the LRMSD metric indicates a deviation. were found. First, AnchoredDesign with only CCD sampling is

PLoS ONE | www.plosone.org 10 June 2011 | Volume 6 | Issue 6 | e20872