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The
successful deciphering of the human genome has highlighted an old challenge
in protein science: for most of the resolved protein sequences we do not know
the corresponding structures and functions. Neither do we understand in
detail the mechanism by which a protein folds into its biologically active
form. Computer experiments offer one way to evaluate the sequence-structure
relationship and the folding process but are extremely difficult for detailed
protein models. This is because the energy landscape of all-atom protein
models is characterized by a multitude of local minima separated by high energy
barriers. Only over the last few years have algorithms been developed that
allow one to overcome this multiple-minima problem in protein simulations.
Prominent examples of these new techniques are parallel tempering and generalized-ensemble
sampling. I will discuss these techniques and ways for their improvement in
the context of simulations of small proteins (of size 30-60 residues). We
study for these molecules the folding mechanism and the relation between
secondary structure formation and folding. Limitations of current energy
functions are discussed. |
References
[1] N.A.
Alves and U.H.E. Hansmann, Phys. Rev. Lett., 84 (2000) 1836. [2]
U.H.E. Hansmann and L. Wille, Phys. Rev. Lett., 88 (2002) 068105. [3] C.-Y.
Lin, C.-K. Hu and U.H.E. Hansmann, Proteins: Structure, Function and Genetics,
52 (2003) 436. [4]
U.H.E. Hansmann, J. Chem. Phys. 120 (2004) 417. [5] W.
Kwak and U.H.E. Hansmann, Phys. Rev. Lett., 95 (2005) 138102 Support
by research grants from the National Science Foundation and the National
Institutes of Health is gratefully acknowledged. |