Molecular modelling study of antigen binding to oxazalone-specific antibodies: The Ox1 idiotypic IgG and its mature variant with increased affinity to 2- phenyloxazolone

Liisa Holm, Leif Laaksonen, Matti Kaartinen, Tuula Teeri, Jonathan Knowles

Research output: Contribution to journalArticleScientificpeer-review

19 Citations (Scopus)

Abstract

Structural models of the variable domains of the murine anti-2-phenyloxazolone IgG (Oxl idiotype) and its somatic variant, which has higher affinity to the hapten 2-phenyloxazolone, were constructed by computer-aided model building using known structures of highly homologous immunoglobulins as templates. Molecular dynamics simulations were used to dock the hapten between the VL and VH domains. The hapten is predicted to bind to slightly different sites in the two models. Hypotheses concerning the role of a number of preferred mutations in anti-oxazolone variants are presented. These can be tested by mutagenesis and crystallography. In particular, the higher binding affinities of the different antibody variants are shown to correlate with better complementarity of electrostatics. The molecular dynamic simulations also suggest that two mobile tryptophans at the mouth of the pocket may play an important role in the binding of hapten.
Original languageEnglish
Pages (from-to)403-409
JournalProtein Engineering
Volume3
Issue number5
DOIs
Publication statusPublished - 1990
MoE publication typeA1 Journal article-refereed

Keywords

  • molecular modelling
  • chemical modelling

Fingerprint Dive into the research topics of 'Molecular modelling study of antigen binding to oxazalone-specific antibodies: The Ox1 idiotypic IgG and its mature variant with increased affinity to 2- phenyloxazolone'. Together they form a unique fingerprint.

  • Cite this