title: Modeling antibody hypervariable loops: a combined algorithm.
abstract: To be of any value, a predicted model of an antibody combining site should have an accuracy approaching that of antibody structures determined by x-ray crystallography (1.6-2.7 A). A number of modeling protocols have been proposed, which fall into two main categories--those that adopt a knowledge-based approach and those that attempt to construct the hypervariable loop regions of the antibody ab initio. Here we present a combined algorithm requiring no arbitrary decisions on the part of the user, which has been successfully applied to the modeling of the individual loops in two systems: the anti-lysozyme antibody HyHel-5, the crystal structure of which is as a complex with lysozyme [Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C. & Davies, D. R. (1987) Proc. Natl. Acad. Sci. USA 84, 8075-8079], and the free antigen binding fragment (Fab) of the anti-lysozyme peptide antibody, Gloop2. This protocol may be used with a high degree of confidence to model single-loop replacements, insertions, deletions, and side-chain replacements. In addition, it may be used in conjunction with other modeling protocols as a method by which to model particular loops whose conformations are predicted poorly by these methods.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, United Kingdom.
authors.forename: A C
authors.initials: AC
authors.lastname: Martin
authors.forename: J C
authors.initials: JC
authors.lastname: Cheetham
authors.forename: A R
authors.initials: AR
authors.lastname: Rees
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex; D007135:Immunoglobulin Variable Region; D007256:Information Systems; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012984:Software
chemical_list: D000936:Antigen-Antibody Complex; D007135:Immunoglobulin Variable Region