title: Contribution of the trifluoroacetyl group in the thermodynamics of antigen-antibody binding.
abstract: We analyzed the binding of the 7C8 antibody to the chloramphenicol phosphonate antigens-one containing a trifluoroacetyl group (CP-F) and the other containing an acetyl group (CP-H)-by using isothermal titration calorimetry (ITC). The thermodynamic difference due to the substitution of F by H was evaluated using free energy calculations based on molecular dynamics (MD) simulations. We have previously shown that another antibody, namely, 6D9, binds more weakly to CP-H than to CP-F, mainly due to the different hydration free energies of the dissociated state and not due to the unfavorable hydrophobic interactions with the antibody in the bound state. Unlike in the binding of the trifluoroacetyl group with 6D9, in its binding with 7C8, it is exposed to the solvent, as seen in the crystal structure of the complex of 7C8 with CP-F. The thermodynamic analysis performed in this study showed that the binding affinity of 7C8 for CP-H is similar to that for CP-F, but this binding to CP-H is accompanied with less favorable enthalpy and more favorable entropy changes. The free energy calculations indicated that, upon the substitution of F by H, enthalpy and entropy changes in the associated and dissociated states were decreased, but the magnitude of enthalpy and entropy changes in the dissociated state was larger than that in the associated state. The differences in binding free energy, enthalpy, and entropy changes determined by the free energy calculations for the substitution of F by H are in good agreement with the experimental results.
authors: Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan. oda@kpu.ac.jp
authors: Masayuki
authors: M
authors: Oda
authors: Minoru
authors: M
authors: Saito
authors: Takeshi
authors: T
authors: Tsumuraya
authors: Ikuo
authors: I
authors: Fujii
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism*; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D017611:Fluorine Compounds / Q000737:chemistry*; D051379:Mice; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D000906:Antibodies; D000941:Antigens; D017611:Fluorine Compounds