Methods of ab initio prediction of amp;agr; helices, amp;bgr; sheets, and polypeptide tertiary structures

摘要

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 &bgr;-sheet structures. Derivation of restraints, detailed atomistic modeling, and a deterministic global optimization method, &agr;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.