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QSAR of multiple mutated antibodies |
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| Authors: | Mandrika Ilona Prusis Peteris Yahorava Sviatlana Tars Kaspars Wikberg Jarl E S |
| Affiliation: | Department of Pharmaceutical Pharmacology, Uppsala University, SE-751 24 Uppasala, Sweden. |
| 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. |
| Keywords: | single chain antibody antibody library QSAR statistical molecular design site directed mutagenesis interaction site mapping amino acid physicochemical properties peptide epitope |
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