A molecular dynamics study based post facto free energy analysis of the binding of bovine angiogenin with UMP and CMP ligands

Angiogenin is a protein belonging to the superfamily of RNase A. The RNase activity of this protein is essential for its angiogenic activity. Although members of the RNase A family carry out RNase activity, they differ marked ly in their strength and specificity. In this paper, we address the problem of higher specificity of angiogenin towards cytosine against uracil in the first base binding position. We have carried out extensive nano-second lev el molecular dynamics(MD) computer simulations on the native bovine angioge nin and on the CMP and UMP complexes of this protein in aqueous medium with explicit molecular solvent. The structures thus generated were subjected t o a rigorous free energy component analysis to arrive at a plausible molecu lar thermodynamic explanation for the substrate specificity of angiogenin.