A MOLECULAR-DYNAMICS APPROACH FOR THE GENERATION OF COMPLETE PROTEIN STRUCTURES FROM LIMITED COORDINATE DATA

Generation of full protein coordinates from limited information, e.g., the C alpha coordinates, is an important step in protein homology mod elling and structure determination, and molecular dynamics (MD) simula tions may prove to be important in this task. We describe a new method , in which the protein backbone is built quickly in a rather crude way and then refined by minimization techniques. Subsequently, the side c hains are positioned using extensive MD calculations. The method is te sted on two proteins, and results compared to proteins constructed usi ng two other MD-based methods. In the first method, we supplemented an existing backbone building method with a new procedure to add side ch ains. The second one largely consists of available methodology. The co nstructed proteins are compared to the corresponding X-ray structures, which became available during this study, and they are in good agreem ent (backbone RMS values of 0.5- 0.7 Angstrom, and all-atom RMS values of 1.5-1.9 Angstrom). This comparative study indicates that extensive MD simulations are able, to some extent, to generate details of the n ative protein structure, and may contribute to the development of a st andardized methodology to predict reliably (parts of) protein structur es when only partial coordinate data are available. (C) 1994 Wiley-Lis s, Inc.