Ž . Biophysical Chemistry 93 2001 181196 Crystallohydrodynamics for solving the hydration problem for multi-domain proteins: open physiological conformations for human IgG Beatriz Carrasco a , Jose Garcia de la Torre a , Kenneth G. Davis b,c , Susan Jones d , Diljeet Athwal e , Chris Walters c , Dennis R. Burton b,f,g , Stephen E. Harding c,  a Departamento de Quimica Fisica, Facultad de Quimica, Uni  ersidad de Murcia, 30071 Murcia, Spain b Krebs Institute, Department of Molecular Biology and Biotechnology, The Uni  ersity, Sheffield S10 2TN, UK c National Centre for Molecular Hydrodynamics, Uni  ersity of Nottingham, School of Biosciences, Sutton Bonington LE12 5RD, UK d Biomolecular Structure and Modelling Unit, Department of Biochemistry and Molecular Biology, Uni  ersity of London, Gower Street, London WC1 6BT, UK e Celltech Therapeutics, Bath Road, Slough, Berkshire SL1 4EN, UK f Department of Immunology, The Scripps Research Institute, North Torrey Pines Road, La Jolla, CA, USA g Department of Molecular Biology, The Scripps Research Institute, North Torrey Pines Road, La Jolla, CA, USA Received 15 May 2001; received in revised form 1 July 2001; accepted 20 July 2001 Abstract Hydrodynamic methods provide a route for studying the low-resolution conformation  in terms of time-averaged spatial orientation of the Fab' and Fc domains relative to each other  of the human IgG subclasses, IgG1, IgG2, IgG3 and IgG4 in the environment in which many exist naturally  a solution. Representative modelling strategies are now available using ‘shell-bead’ or ‘shell’ modelling of the surface of the molecules with the size-independent  Ž .  programme SOLPRO J. Garcia de la Torre, S.E. Harding, B. Carrasco, Eur. Biophys. J. 28 1999 119 132 . The shell model fits to the equivalent inertial surface ellipsoids of the published crystal structures for the Fab' and Fc domains of IgG are made and an apparent hydration  of 0.51gg for Fab' and 0.70 gg for the glycoprotein Fc app Ž . Ž . are obtained, which yield an average value of 0.59 0.07 gg for the intact antibody 2 Fab' 1 Fc . The relative Ž orientations of these domains for each of the IgG subclasses is then found using where appropriate a cylindrical . Ž . hinge from SOLPRO by modelling the Perrin function, P i.e. ‘frictional ratio due to shape’ using this  and app experimentally measured sedimentation coefficients. All the IgG subclasses appear as open, rather than compact  Corresponding author. Tel.: 44-115-951-6148; fax: 44-115-951-6142. Ž . E-mail address: steve.harding@nottingham.ac.uk S.E. Harding . 0301-462201$ - see front matter  2001 Elsevier Science B.V. All rights reserved. Ž . PII: S 0 3 0 1 - 4 6 2 2 01 00220-4