QSAR of multiple mutated antibodies

J Mol Recognit. 2007 Mar-Apr;20(2):97-102. doi: 10.1002/jmr.817.

Abstract

The aim of this study was to develop predictive quantitative structure-activity relationship (QSAR) modeling for antibody-peptide interactions. A small single chain antibody library was designed and manufactured around the murine anti-p24 (HIV-1) monoclonal antibody CB4-1 by use of statistical molecular design (SMD) principles and site directed mutagenesis, and its affinity for a p24 derived antigen was determined by fluorescence polarization. A satisfactory QSAR model (Q(2) = 0.74, R(2) = 0.88) was derived by correlating the affinity data to physicochemical property scales of the amino acids varied in the library. The model explains most of the antibody-antigen interactions of the studied set, and provides insights into the molecular mechanism involved in antigen binding.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / immunology
  • Animals
  • Antibodies / analysis*
  • Antibodies / genetics*
  • Antibodies / metabolism
  • HIV Core Protein p24 / chemistry
  • HIV Core Protein p24 / immunology
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Models, Molecular
  • Models, Theoretical
  • Mutant Proteins / analysis*
  • Mutation
  • Peptide Library
  • Quantitative Structure-Activity Relationship*
  • Single-Chain Antibodies

Substances

  • Antibodies
  • HIV Core Protein p24
  • Immunoglobulin Variable Region
  • Mutant Proteins
  • Peptide Library
  • ScFv CB4-1
  • Single-Chain Antibodies