A generalized-ensemble technique, multicanonical sampling, is used to study the folding of a 34-residue human parathyroid hormone fragment. An all-atom model of the peptide is employed and the protein–solvent interactions are approximated by an implicit solvent. Our results demonstrate that generalized-ensemble simulations are well suited to sample low-energy structures of such large polypeptides. Configurations with a root-mean-square deviation to the crystal structure of less than 1 Å are found. Finally, we discuss limitations of our implicit solvent model.
REFERENCES
1.
P.
Ferrara
and A.
Caflisch
, Proc. Natl. Acad. Sci. U.S.A.
97
, 10780
(2000
).2.
3.
Sh.
Chowdhury
, W.
Zhang
, Ch.
Wu
, G.
Xiong
, and Y.
Duan
, Biopolymers
68
, 63
(2003
).4.
U. H. E.
Hansmann
and Y.
Okamoto
, Curr. Opin. Struct. Biol.
9
, 177
(1999
).5.
6.
A. E.
Cardenas
and R.
Elber
, Proteins: Struct., Funct., Genet.
51
, 245
(2003
).7.
8.
A. E.
Garcia
and K. Y.
Sabonmatsu
, Proteins: Struct., Funct., Genet.
42
, 345
(2001
).9.
C.-Y.
Lin
, C.-K.
Hu
, and U. H. E.
Hansmann
, Proteins: Struct., Funct., Genet.
52
, 436
(2003
).10.
11.
U. H. E. Hansmann and Y. Okamoto, in Annual Reviews in Computational Physics VI, edited by D. Stauffer (World Scientific, Singapore, 1998), p. 129.
12.
13.
14.
15.
16.
W.
Klaus
, T.
Dieckmann
, V.
Wray
, D.
Schomburg
, E.
Wingender
, and H.
Mayer
, Biochemistry
30
, 6936
(1991
).17.
L.
Jin
, S. L.
Briggs
, S.
Chandrasekhar
, N. Y.
Chirgadze
, D. K.
Clawson
, R. W.
Schevitz
, D. L.
Smiley
, A. H.
Tashjian
, and F.
Zhang
, J. Biol. Chem.
275
, 27238
(2000
).18.
U. C.
Marx
, K.
Adermann
, P.
Bayer
, W.-G.
Forssmann
, and P.
Rösch
, Biochem. Biophys. Res. Commun.
267
, 213
(2000
).19.
J. T.
Potts
, Jr., H. M.
Kronenberg
, and M.
Rosenblatt
, Adv. Protein Chem.
35
, 323
(1982
).20.
R.
Brommage
, C. E.
Hotchkiss
, C. J.
Lees
, M. W.
Stancill
, J. M.
Hock
, and C. P.
Jerome
, J. Clin. Endocrinol. Metab.
84
, 3757
(1999
).21.
Y.
Okamoto
, T.
Kikuchi
, T.
Nakazawa
, and H.
Kawai
, Int. J. Pept. Protein Res.
42
, 300
(1993
).22.
G.
Némethy
, K. D.
Gibson
, K. A.
Palmer
, C.-N.
Yoon
, G.
Paterlini
, A.
Zagari
, S.
Rumsey
, and H. A.
Scheraga
, J. Phys. Chem.
96
, 6472
(1992
).23.
T.
Ooi
, M.
Obatake
, G.
Nemethy
, and H. A.
Scheraga
, Proc. Natl. Acad. Sci. U.S.A.
8
, 3086
(1987
).24.
F.
Eisenmenger
, U. H. E.
Hansmann
, Sh.
Hayryan
, and C.-K.
Hu
, Comput. Phys. Commun.
138
, 192
(2001
).25.
A. M.
Ferrenberg
and R. H.
Swendsen
, Phys. Rev. Lett.
61
, 2635
(1988
);A. M.
Ferrenberg
and R. H.
Swendsen
, Phys. Rev. Lett.
63
, 1658
(E) (1989
), and references given in the erratum.26.
27.
F.
Eisenhaber
, P.
Lijnzaad
, P.
Argos
, C.
Sander
, and M.
Scharf
, J. Comput. Chem.
16
, 273
(1995
).28.
T.
Schaumann
, W.
Braun
, and K.
Wuthrich
, Biopolymers
29
, 679
(1990
).29.
U. H. E.
Hansmann
and L.
Wille
, Phys. Rev. Lett.
88
, 068105
(2002
).
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