title: Conformation-controlled binding kinetics of antibodies.
abstract: Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Fisica e Astronomia and CSDC, via G. Sansone 1, IT-50019 Sesto Fiorentino, Firenze, Italia.|Dipartimento di Sistemi e Informatica, Università di Firenze, Via S. Marta 3, IT-50139 Florence, Italy.|INFN, Sezione di Firenze, Italia.|Université d'Orléans, Centre de Biophysique Moléculaire, CNRS-UPR4301, Rue C. Sadron, 45071, Orléans, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Galanti
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Fisica e Astronomia and CSDC, via G. Sansone 1, IT-50019 Sesto Fiorentino, Firenze, Italia.|INFN, Sezione di Firenze, Italia.
authors.forename: Duccio
authors.initials: D
authors.lastname: Fanelli
authors.affiliation: Université d'Orléans, Centre de Biophysique Moléculaire, CNRS-UPR4301, Rue C. Sadron, 45071, Orléans, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piazza
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D001665:Binding Sites; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions
chemical_list: D000906:Antibodies; D012996:Solutions