title: Multi-scale calculation and global-fit analysis of hydrodynamic properties of biological macromolecules: determination of the overall conformation of antibody IgG molecules.
abstract: We present a scheme, based on existing and newly developed computational tools, for the determination of the overall conformation of biological macromolecules composed by domains or subunits, using from such structural determination easily available solution properties. In a multi-scale approach, atomic-level structures are used to provide simple shapes for the subunits, which are put together in a coarse grained model, with a few parameters that determine the overall shape of the macromolecule. Computer programs, like those in the HYDRO suite that evaluate the properties of either atomic or coarse-grained models. In this paper we present a new scheme for a global fit of multiple properties, implemented in a new computer program, HYDROFIT, which interfaces with the programs of the HYDRO suite to find an optimum, best-fitting structure in a robust but simple way. The determination of the overall structure of the native antibody IgG3, bearing a long hinge, and that of the hingeless mutant m15 is presented to test and confirm the validity of this simple, systematic and efficient scheme.
authors.affiliation: Departamento de Química-Física, Facultad de Química, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Amorós
authors.forename: A
authors.initials: A
authors.lastname: Ortega
authors.forename: S E
authors.initials: SE
authors.lastname: Harding
authors.forename: J
authors.initials: J
authors.lastname: García de la Torre
mesh_terms: D003201:Computers; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000235:genetics; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics; D007074:Immunoglobulin G / Q000737:chemistry* / Q000235:genetics; D008956:Models, Chemical; D009154:Mutation; D011487:Protein Conformation; D012984:Software; D014867:Water / Q000737:chemistry
chemical_list: D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D014867:Water