STOCHASTICOPTIMIZATION METHODS FOR PROTEIN FOLDING
We recently developed an all-atom free energy force field (PFF01) for protein structure prediction with stochastic optimization methods. We demonstrated that PFF01 correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size.
KeywordsPotential Energy Surface Free Energy Surface Native Conformation Protein Structure Prediction Secondary Structure Content
Unable to display preview. Download preview PDF.
- 7.C. B. Anfinsen. Principles that govern the folding of protein chains. Science, 181:223–230, 1973.Google Scholar
- 8.Z. Li and H. A. Scheraga. Monte carlo minimization approach to the multipleminima problem in protein folding. Proc. Nat. Acad. Sci. U.S.A., 84:6611–6615, 1987.Google Scholar
- 10.T. Herges and W. Wenzel. Reproducible in-silico folding of a three-helix protein in a transferable all-atom force field. Physical Review Letters (in press), http://www.arXiv.org: physics/0310146, 2004.
- 13.A. Schug, T. Herges, and W. Wenzel. All-atom folding of the three-helix hiv accessory protein with an adaptive parallel tempering method. Proteins (in press), 2004.Google Scholar
- 14.A. Schug, T. Herges, and W. Wenzel. Reproducible folding of a four helix protein in an all-atom force field. J. Am. Chem. Soc. (in press), 2004.Google Scholar
- 26.G. J. Geyer. Stat. Sci., 7:437, 1992.Google Scholar
- 33.S. Kirkpatrick, C. D. Gelatt, and M. P. Vecchi. Optimization by simulated annealing. Science, 220:671–680, 1983.Google Scholar
- 35.A. Schug, A. Verma, T. Herges, and W. Wenzel. Comparison of stochastic optimization methods for all-atom folding of the trp-cage protein. submitted to Proteins, 2005.Google Scholar