• Media type: E-Article
  • Title: Modeling Antibody Hypervariable Loops: A Combined Algorithm
  • Contributor: Cheetham, Janet C.; Rees, Anthony R.
  • Published: National Academy of Sciences of the United States of America, 1989
  • Published in: Proceedings of the National Academy of Sciences of the United States of America, 86 (1989) 23, Seite 9268-9272
  • Language: English
  • ISSN: 0027-8424
  • Origination:
  • Footnote:
  • Description: 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 angstrom). 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 nati-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.
  • Access State: Open Access