Relative binding free energy calculations of DNA to daunomycin and its 13-dihydro analogue.

We present the results of thermodynamic integration/molecular dynamics on the 13-dihydrodaunomycin.d(CGTACG) complex and 13-dihydrodaunomycin in vacuo based on the GROMOS force field. The objective is to calculate the binding free energy differences between two complexes--13-dihydrodaunomycin.d(CGTACG) and daunomycin.d(CGTACG). The results are in agreement with the experimental data, i.e. the theoretical binding free energy difference of 13-dihydrodaunomycin.d(CGTACG) and daunomycin.d(CGTACG) is 2.1 +/- 1.6 kcal/mol which accords well with the experimental value of 0.6 kcal/mol. The free energy contributions of different interactions and different groups have also been analysed.