Calculation of Relative Binding of Free Energy of Vancomycin with Diacetyl-L-Lysyl-D-Alanyl-D-Alanine and Diacetyl-L-Lysyl-L-Alanyl-L-Alanine

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By means of a free energy perturbation method implemented with molecular dynamics, the relative binding of free energies of vancomycin with Ac_2-L-LYs-D-Ala-D-Ala and with Ac_2-L-Lys-L-Ala-L-Ala peptide ligands were calculated. A transition state between the vancomycin complex with the D-form peptide and the complex with the L-form peptide was employed as the perturbation final stage in order to overcome the difficulties of calculateg the perturbation between isomers. The calculated relative binding of free energy was 5.15 kcal/mol in water, which compared well with an experimental value of 8.4 kcal/mol. Structure analysis were performed on the number of possible hydrogen bondings, the hydrophobic interactions between peptide ligands and vancomycin, and the bonding angle between designated nuclei. The calculated structure results were all well suported by the NMR data. An investigation of the relative free energy calculation suggests that relative binding affinity in a host-guest system can be achieved by molecular dynamic simulation and the finite difference thermodynamic intergation method.
公益社団法人日本生物工学会の論文
1995-08-25