Modeling of angiogenin-3 '-NMP complex

Angiogenin belongs to the Ribonuclease superfamily and has a weak enzymatic activity that is crucial for its biological function of stimulating blood vessel growth. Structural studies on ligand bound Angiogenin will go a long way in understanding the mechanism of the protein as well as help in desig ning drugs against it. In this study we present the first available structu re of nucleotide ligand bound Angiogenin obtained by computer modeling. The importance of this study in itself notwithstanding, is a precursor to mode ling a full dinucleotide substrate onto Angiogenin. Bovine Angiogenin, the structure of which has been solved at a high resolution, was earlier subjec ted to Molecular Dynamics simulations for a nanosecond. The MD structures o ffer better starting points for docking as they offer lesser obstruction th an the crystal structure to ligand binding. The MD structure with the least serious short contacts was modeled to obtain a steric free Angiogenin - 3' mononucleotide complex structure. The structures were energetically minimi zed and subjected to a brief spell of Molecular Dynamics. The results of th e simulation show that all the li,ligand-Angiogenin interactions and hydrog en bonds are retained, redeeming the structure and docking procedure. Furth er, following ligand - protein interactions in the case of the ligands 3'-C MP and 3'-UMP we were able to speculate on how Angiogenin, a predominantly prymidine specific ribonuclease prefers Cytosine to Uracil in the first bas e position.