PREDICTION OF THE CONFORMATION AND STABILITY OF MACROMOLECULAR STRUCTURES

摘要

A method is provided for determining the time-average conformation and the packing energy of a macromolecular structure such as a peptide or nucleic acid. Using conformation probability maps, multiple peptide side chains are rotated to many different conformations. At each conformation, the interaction energy of each peptide side chain with its neighbors is determined and used to refine a conformation energy map. After repeated rotational moves, the method produces, for each side chain, a complete conformation energy map which is then used to determine a conformation probability map. The new conformation probability map replaces the previous one and a new cycle is started. This process drives the macromolecular structure to a final self-consistent ensemble of probable conformations representing a time-average structure of the actual macromolecule. The free energy of the structure can also be determined. The method may be employed to identify the stability of mutant peptides.