Molecular dynamics simulations of hapten binding to structural models of 2-phenyloxazolone antibodies

Structural models of an anti-2-phenyloxazolone (Ox1) idiotype and its high-affinity variant NQ22/18.7 were constructed by computer-aided molecular modeling using known structures of highly homologous immunoglobulins as templates. Hapten binding was studied by manual docking of the hapten into the Ox1 idiotype model and into the high-affinity variant NQ22/18.7. The position and orientation of the hapten were refined by molecular dynamics simulations. The stochastic boundary molecular dynamics method was used to study the detailed structural and dynamic properties of the hapten binding site and the effects of solvent on these properties. Hapten binding is predicted to differ slightly in these two antibody-hapten complexes. The modeled structures of the idiotype Ox1 antibody and its variant are in good agreement with the experimentally determined structure of a related anti-2-phenyloxazolone antibody, NQ10/12.5