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

Fingerprint

Molecular modeling
Haptens
Antigens
Antibodies
Immunoglobulin G
Molecular dynamics
Molecular Dynamics Simulation
Mutagenesis
Docks
Crystallography
Computer simulation
Oxazolone
Antibody Affinity
Electrostatics
Structural Models
Static Electricity
Tryptophan
Computer Simulation
Mouth
Immunoglobulins

Keywords

  • molecular modelling
  • chemical modelling

Cite this

Holm, Liisa ; Laaksonen, Leif ; Kaartinen, Matti ; Teeri, Tuula ; Knowles, Jonathan. / Molecular modelling study of antigen binding to oxazalone-specific antibodies: The Ox1 idiotypic IgG and its mature variant with increased affinity to 2- phenyloxazolone. In: Protein Engineering. 1990 ; Vol. 3, No. 5. pp. 403-409.
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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.",
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Molecular modelling study of antigen binding to oxazalone-specific antibodies: The Ox1 idiotypic IgG and its mature variant with increased affinity to 2- phenyloxazolone. / Holm, Liisa; Laaksonen, Leif; Kaartinen, Matti; Teeri, Tuula; Knowles, Jonathan.

In: Protein Engineering, Vol. 3, No. 5, 1990, p. 403-409.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Molecular modelling study of antigen binding to oxazalone-specific antibodies: The Ox1 idiotypic IgG and its mature variant with increased affinity to 2- phenyloxazolone

AU - Holm, Liisa

AU - Laaksonen, Leif

AU - Kaartinen, Matti

AU - Teeri, Tuula

AU - Knowles, Jonathan

PY - 1990

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N2 - 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.

AB - 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.

KW - molecular modelling

KW - chemical modelling

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DO - 10.1093/protein/3.5.403

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SN - 1741-0126

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ER -