title: Immunoglobulin Structure Exhibits Control over CDR Motion.
abstract: Motions of the IgG structure are evaluated using normal mode analysis of an elastic network model to detect hinges, the dominance of low frequency modes, and the most important internal motions. One question we seek to answer is whether or not IgG hinge motions facilitate antigen binding. We also evaluate the protein crystal and packing effects on the experimental temperature factors and disorder predictions. We find that the effects of the protein environment on the crystallographic temperature factors may be misleading for evaluating specific functional motions of IgG. The extent of motion of the antigen binding domains is computed to show their large spatial sampling. We conclude that the IgG structure is specifically designed to facilitate large excursions of the antigen binding domains. Normal modes are shown as capable of computationally evaluating the hinge motions and the spatial sampling by the structure. The antigen binding loops and the major hinge appear to behave similarly to the rest of the structure when we consider the dominance of the low frequency modes and the extent of internal motion. The full IgG structure has a lower spectral dimension than individual Fabdomains, pointing to more efficient information transfer through the antibody than through each domain. This supports the claim that the IgG structure is specifically constructed to facilitate antigen binding by coupling motion of the antigen binding loops with the large scale hinge motions.
authors.affiliation: L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA 50011, USA ; Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA ; Bioinformatics and Computational Biology, Iowa State University, Ames, IA 50011, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Zimmermann
authors.affiliation: L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA 50011, USA.
authors.forename: Aris
authors.initials: A
authors.lastname: Skliros
authors.affiliation: L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA 50011, USA ; Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA ; Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH 43205, USA ; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kloczkowski
authors.affiliation: L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, IA 50011, USA ; Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA ; Bioinformatics and Computational Biology, Iowa State University, Ames, IA 50011, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jernigan