MOLECULAR-DYNAMICS SIMULATION OF EGF AND TGF-ALPHA - CONFORMATION ANDRECEPTOR-BINDING PROPERTIES

Three 1 ns-long molecular dynamics (MD) simulations were performed on murine epidermal growth factor (mEGF), human epidermal growth factor ( hEGF) and human transforming growth factor-alpha (hTGF-alpha) to obtai n further information about their conformational properties. The initi al structures were taken based on NMR spectroscopy data and were energ y-minimized before MD simulations. No major conformational transitions were observed during simulations. Domain movements, predictable from the mitten model of EGF, were observed only in the simulation of hTGF- alpha and could account for its different receptor binding properties. Inter-domain interactions, not revealed by the NMR data, were observe d between aromatic side-chains for each of the polypeptides and seem t o stabilize the conformation necessary for binding. (C) 1997 Elsevier Science B.V.