Comparison of the dynamics of bovine and human angiogenin: A molecular dynamics study

Molecular dynamics simulations have been carried out for I ns on human and bovine angiogenin systems in an effort to compare and contrast their dynami cs. An analysis of their dynamics is done by examining the mts deviations, following hydrogen-bonding interactions and looking at the role of water in and around the protein. The C-terminus of bovine angiogenin moves apprecia bly during dynamics suggesting a better structure for ligand binding. Howev er, we do not Smd any evidence of a conformation where the glutamate residu e that obstructs the active site takes on a different conformation. We obse rve a differential hydrogen-bonding pattern in the active site regions of b ovine and human angiogenins, which could have a bearing on the different ca talytic activities of the the proteins. We also propose that the differenti al binding of the monoclonal antibody toward the two proteins might be due sequential and not conformational differences. Water molecules might play a n important functional role in both proteins given their subtle functional differences. A simple computation on the molecular dynamics data has been c arried out to identify locations in and around the protein that are invaria bly occupied by water. The locations of nearly half the waters we have iden tified from the simulation as being invariant in bovine angiogenin occupy s imilar locations in the bovine angiogenin crystal structure. The positions of the waters identified in human angiogenin differ considerably from that of bovine angiogenin. (C) 1999 John Wiley & Sons, Inc.