Abstract: The binding free energy of human C3c-Compstatin complex was calculated by an MM/PBSA method, and the key residues interactions were also investigated between MG4-MG5 binding domain of C3c and Compstatin by using energy decomposition method.The results showed that the calculated binding free energy(-8.06 kcal/mol)was in high agreement with the binding affinity(-6.72 kcal/mol)by the experimental essays,the total energy in the molecule(-177.24 kcal/mol)showing the maximal contribution to binding complement inhibitor,followed by vaccum electrostatic interaction(-108.74 kcal/mol)and Van der Waals interaction(-68.51 kcal/mol). The dynamic process of combination between C3c and the inhibitor together with the changes of the protein under the effect of combination was simulated as a complementary part in the crystal experiments.Our molecular dynamics stimulation proved the experiment with the structure information:Residue ARG459,ASP491,MET457 of C3c and TRP7,TRP4,HIS10 of Compstatin had major contribution to the binding free energy of the complex.The information above provides some insights into the based structural design of inhibitor of complement 3.
2013, Vol. 28 
