2.3 Simulation Notes
1. Missing residues, especially the residues on the CH1-1 loop,
are important for allosteric effects. Thus, these missing residues
should be reconstructed.
2. The initially constructed structures may contain some unreasonable steric overlaps between sidechains and backbones. The
SD minimization with CHARMM36 force field is required to
eliminate any bad atom contact. To minimize the structural
disruption of the complex, especially the residues on the
antibody-antigen interface, the hydrogen bonds and salt
bridges are harmoniously constrained during the SD
minimization.
3. The crystallized interfacial water molecules are crucial for the
antibody-antigen recognition. When constructing the systems,
these crystallized water molecules should not be excluded.
4. For cluster analysis, RMSD and Rg data for each structure in
the equilibrium trajectories are calculated. The structures with
the RMSD and Rg difference less than 4 A ˚
´ are assigned as the
same cluster.
5. Correlation analysis (Cij) of the motion required both simulation conformations and initial crystal conformations, thus the
more conformations considered, the more accurate of the
motion correlation analysis.
6. During the network analysis, the oxygen of the water molecules
should be renamed to CA in order to be recognized by “network view” program.
7. The sub-optimal path (default is 20) evaluation should be set
up carefully. In some cases when the complex is large, the
sub-optimal path should set up <20, or there will be unexpected long time to evaluate all the possible sub-optimal path.
Acknowledgements
This project has been funded in whole or in part with Federal funds
from the National Cancer Institute, National Institutes of Health,
under contract number HHSN261200800001E. This research was
supported (in part) by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. JZ
was supported in part by the Intramural Research Program of the
NIH, NIDCD.
References
1. Wei G, Xi W, Nussinov R, Ma B (2016) Protein
ensembles: how does nature harness thermodynamic fluctuations for life? The diverse functional roles of conformational ensembles in the
cell. Chem Rev 116(11):6516–6551. https://
doi.org/10.1021/acs.chemrev.5b00562
2. Gunasekaran K, Ma B, Nussinov R (2004) Is
allostery an intrinsic property of all dynamic
proteins? Proteins 57(3):433–443
3. Hu Z, Bowen D, Southerland WM, del Sol A,
Pan Y, Nussinov R, Ma B (2007) Ligand binding and circular permutation modify residue
The Allosteric Effect in Antibody-Antigen Recognition
181
1. Missing residues, especially the residues on the CH1-1 loop,
are important for allosteric effects. Thus, these missing residues
should be reconstructed.
2. The initially constructed structures may contain some unreasonable steric overlaps between sidechains and backbones. The
SD minimization with CHARMM36 force field is required to
eliminate any bad atom contact. To minimize the structural
disruption of the complex, especially the residues on the
antibody-antigen interface, the hydrogen bonds and salt
bridges are harmoniously constrained during the SD
minimization.
3. The crystallized interfacial water molecules are crucial for the
antibody-antigen recognition. When constructing the systems,
these crystallized water molecules should not be excluded.
4. For cluster analysis, RMSD and Rg data for each structure in
the equilibrium trajectories are calculated. The structures with
the RMSD and Rg difference less than 4 A ˚
´ are assigned as the
same cluster.
5. Correlation analysis (Cij) of the motion required both simulation conformations and initial crystal conformations, thus the
more conformations considered, the more accurate of the
motion correlation analysis.
6. During the network analysis, the oxygen of the water molecules
should be renamed to CA in order to be recognized by “network view” program.
7. The sub-optimal path (default is 20) evaluation should be set
up carefully. In some cases when the complex is large, the
sub-optimal path should set up <20, or there will be unexpected long time to evaluate all the possible sub-optimal path.
Acknowledgements
This project has been funded in whole or in part with Federal funds
from the National Cancer Institute, National Institutes of Health,
under contract number HHSN261200800001E. This research was
supported (in part) by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. JZ
was supported in part by the Intramural Research Program of the
NIH, NIDCD.
References
1. Wei G, Xi W, Nussinov R, Ma B (2016) Protein
ensembles: how does nature harness thermodynamic fluctuations for life? The diverse functional roles of conformational ensembles in the
cell. Chem Rev 116(11):6516–6551. https://
doi.org/10.1021/acs.chemrev.5b00562
2. Gunasekaran K, Ma B, Nussinov R (2004) Is
allostery an intrinsic property of all dynamic
proteins? Proteins 57(3):433–443
3. Hu Z, Bowen D, Southerland WM, del Sol A,
Pan Y, Nussinov R, Ma B (2007) Ligand binding and circular permutation modify residue
The Allosteric Effect in Antibody-Antigen Recognition
181