The present invention provides a novel four stage ab initio approach for
predicting the tertiary structure of polypeptides. The methods of the
invention combine the classical and modern views of protein folding, while
using free energy calculations and integer linear optimization to predict
helical and .beta.-sheet structures. Derivation of restraints, detailed
atomistic modeling, and a deterministic global optimization method,
.alpha.BB, coupled with torsion angle dynamics, form the basis for the
final tertiary structure prediction. The performance of the methods of the
invention is illustrated using several different polypeptides.
