In this paper, we report results of using enhanced sampling and blind selection techniques for high-accuracy protein structural refinement. By combining a parallel continuous simulated tempering (PCST) method, previously developed by Zang et al. [J. Chem. Phys. 141, 044113 (2014)], and the structure based model (SBM) as restraints, we refined 23 targets (18 from the refinement category of the CASP10 and 5 from that of CASP12). We also designed a novel model selection method to blindly select high-quality models from very long simulation trajectories. The combined use of PCST-SBM with the blind selection method yielded final models that are better than initial models. For Top-1 group, 7 out of 23 targets had better models (greater global distance test total scores) than the critical assessment of structure prediction participants. For Top-5 group, 10 out of 23 were better. Our results justify the crucial position of enhanced sampling in protein structure prediction and refinement and demonstrate that a considerable improvement of low-accuracy structures is achievable with current force fields.
REFERENCES
1.
Y.
Zhang
, Curr. Opin. Struct. Biol.
18
(3
), 342
(2008
).2.
E.
Faraggi
, Y.
Yang
, S.
Zhang
, and Y.
Zhou
, Structure
17
(11
), 1515
(2009
).3.
Y.
Zhang
, BMC Bioinf.
9
(1
), 40
(2008
).4.
S.
Raman
, R.
Vernon
, J.
Thompson
, M.
Tyka
, R.
Sadreyev
, J.
Pei
, D.
Kim
, E.
Kellogg
, F.
DiMaio
, O.
Lange
, L.
Kinch
, W.
Sheffler
, B.-H.
Kim
, R.
Das
, N. V.
Grishin
, and D.
Baker
, Proteins: Struct., Funct., Bioinf.
77
(S9
), 89
(2009
).5.
M. A.
Marti-Renom
, A. C.
Stuart
, A.
Fiser
, R.
Sanchez
, F.
Melo
, and A.
Sali
, Annu. Rev. Biophys. Biomol. Struct.
29
, 291
(2000
).6.
J.
Peng
and J.
Xu
, Proteins
79
(Suppl. 10
), 161
(2011
).7.
S. T.
Wu
, J.
Skolnick
, and Y.
Zhang
, BMC Biol.
5
, 17
(2007
).8.
Y. J.
Huang
, B.
Mao
, J. M.
Aramini
, and G. T.
Montelione
, Proteins
82
(Suppl. 2
), 43
(2014
).9.
V.
Mariani
, F.
Kiefer
, T.
Schmidt
, J.
Haas
, and T.
Schwede
, Proteins: Struct., Funct., Bioinf.
79
(S10
), 37
(2011
).10.
J.
Moult
, K.
Fidelis
, A.
Kryshtafovych
, T.
Schwede
, and A.
Tramontano
, Proteins: Struct., Funct., Bioinf.
82
, 1
(2014
).11.
J.
Moult
, J. T.
Pedersen
, R.
Judson
, and K.
Fidelis
, Proteins: Struct., Funct., Genet.
23
(3
), ii
(1995
).12.
J.
Moult
, Curr. Opin. Struct. Biol.
15
(3
), 285
(2005
).13.
T.
Nugent
, D.
Cozzetto
, and D. T.
Jones
, Proteins: Struct., Funct., Bioinf.
82
, 98
(2014
).14.
J. L.
MacCallum
, A.
Perez
, M. J.
Schnieders
, L.
Hua
, M. P.
Jacobson
, and K. A.
Dill
, Proteins
79
(Suppl. 10
), 74
(2011
).15.
K.
Lindorff-Larsen
, S.
Piana
, R. O.
Dror
, and D. E.
Shaw
, Science
334
(6055
), 517
(2011
).16.
S.
Piana
, K.
Lindorff-Larsen
, and D. E.
Shaw
, Proc. Natl. Acad. Sci. U. S. A.
109
(44
), 17845
(2012
).17.
T.
Zang
, L.
Yu
, C.
Zhang
, and J.
Ma
, J. Chem. Phys.
141
(4
), 044113
(2014
).18.
P. C.
Whitford
, J. K.
Noel
, S.
Gosavi
, A.
Schug
, K. Y.
Sanbonmatsu
, and J. N.
Onuchic
, Proteins: Struct., Funct., Bioinf.
75
(2
), 430
(2009
).19.
C.
Clementi
, H.
Nymeyer
, and J. N.
Onuchic
, J. Mol. Biol.
298
(5
), 937
(2000
).20.
A.
Zemla
, C.
Venclovas
, J.
Moult
, and K.
Fidelis
, Proteins: Struct., Funct., Genet.
37
(Suppl. 3
), 22
–29
(1999
).21.
A.
Zemla
, Č.
Venclovas
, J.
Moult
, and K.
Fidelis
, Proteins: Struct., Funct., Genet.
45
(Suppl. 5
), 13
(2001
).22.
A.
Zemla
, Nucleic Acids Res.
31
(13
), 3370
(2003
).23.
A.
Mitsutake
, Y.
Sugita
, and Y.
Okamoto
, Biopolymers
60
(2
), 96
(2001
).24.
B. A.
Berg
and T.
Neuhaus
, Phys. Rev. Lett.
68
(1
), 9
(1992
).25.
B.
Baumann
, Nucl. Phys. B
285
(3
), 391
(1987
).26.
F. G.
Wang
and D. P.
Landau
, Phys. Rev. Lett.
86
(10
), 2050
(2001
).27.
P.
Dayal
, S.
Trebst
, S.
Wessel
, D.
Wurtz
, M.
Troyer
, S.
Sabhapandit
, and S. N.
Coppersmith
, Phys. Rev. Lett.
92
(9
), 097201
(2004
).28.
Q. L.
Yan
, R.
Faller
, and J. J.
de Pablo
, J. Chem. Phys.
116
(20
), 8745
(2002
).29.
Q. L.
Yan
and J. J.
de Pablo
, Phys. Rev. Lett.
90
(3
), 035701
(2003
).30.
M. S.
Shell
, P. G.
Debenedetti
, and A. Z.
Panagiotopoulos
, Phys. Rev. E
66
(5
), 056703
(2002
).31.
E.
Marinari
and G.
Parisi
, Europhys. Lett.
19
(6
), 451
(1992
).32.
R. H.
Swendsen
and J. S.
Wang
, Phys. Rev. Lett.
57
(21
), 2607
(1986
).33.
M.
Falcioni
and M. W.
Deem
, J. Chem. Phys.
110
(3
), 1754
(1999
).34.
Y.
Sugita
and Y.
Okamoto
, Chem. Phys. Lett.
314
(1-2
), 141
(1999
).35.
D. J.
Earl
and M. W.
Deem
, Phys. Chem. Chem. Phys.
7
(23
), 3910
(2005
).36.
P.
Jiang
, F.
Yasar
, and U. H. E.
Hansmann
, J. Chem. Theory Comput.
9
(8
), 3816
(2013
).37.
C.
Zhang
and J. P.
Ma
, J. Chem. Phys.
130
(19
), 194112
(2009
).38.
C.
Zhang
and J. P.
Ma
, J. Chem. Phys.
132
(24
), 244101
(2010
).39.
G.
Bussi
, F. L.
Gervasio
, A.
Laio
, and M.
Parrinello
, J. Am. Chem. Soc.
128
(41
), 13435
(2006
).40.
C.
Camilloni
, D.
Provasi
, G.
Tiana
, and R. A.
Broglia
, Proteins
71
(4
), 1647
(2008
).41.
A.
Barducci
, M.
Bonomi
, M. K.
Prakash
, and M.
Parrinello
, Proc. Natl. Acad. Sci. U. S. A.
110
(49
), E4708
(2013
).42.
R.
Zhou
, B. J.
Berne
, and R.
Germain
, Proc. Natl. Acad. Sci. U. S. A.
98
(26
), 14931
(2001
).43.
A.
Plazinska
, W.
Plazinski
, and K.
Jozwiak
, J. Comput. Chem.
35
(11
), 876
(2014
).44.
A. E.
García
and J. N.
Onuchic
, Proc. Natl. Acad. Sci. U. S. A.
100
(24
), 13898
(2003
).45.
G. M.
Torrie
and J. P.
Valleau
, J. Comput. Phys.
23
(2
), 187
(1977
).46.
C.
Bartels
and M.
Karplus
, J. Phys. Chem. B
102
(5
), 865
(1998
).47.
A.
Laio
and M.
Parrinello
, Proc. Natl. Acad. Sci. U. S. A.
99
(20
), 12562
(2002
).48.
A.
Barducci
, G.
Bussi
, and M.
Parrinello
, Phys. Rev. Lett.
100
(2
), 020603
(2008
).49.
J. K.
Noel
, P. C.
Whitford
, and J. N.
Onuchic
, J. Phys. Chem. B
116
(29
), 8692
(2012
).50.
C.
Zhang
and J.
Ma
, Proc. Natl. Acad. Sci. U. S. A.
109
(21
), 8139
(2012
).51.
J.
Shao
, S. W.
Tanner
, N.
Thompson
, and T. E.
Cheatham
, J. Chem. Theory Comput.
3
(6
), 2312
(2007
).52.
A.
Raval
, S.
Piana
, M. P.
Eastwood
, R. O.
Dror
, and D. E.
Shaw
, Proteins: Struct., Funct., Bioinf.
80
(8
), 2071
(2012
).53.
J.
Zhang
and Y.
Zhang
, PLoS One
5
(10
), e15386
(2010
).54.
C.
Zhang
, S.
Liu
, Q.
Zhu
, and Y.
Zhou
, J. Med. Chem.
48
(7
), 2325
(2005
).55.
H.
Zhou
and J.
Skolnick
, Biophys. J.
101
(8
), 2043
(2011
).56.
M.
Lu
, A. D.
Dousis
, and J.
Ma
, J. Mol. Biol.
376
(1
), 288
(2008
).57.
H. J. C.
Berendsen
, D.
Vanderspoel
, and R.
Vandrunen
, Comput. Phys. Commun.
91
(1-3
), 43
(1995
).58.
E.
Lindahl
, B.
Hess
, and D.
van der Spoel
, J. Mol. Model
7
(8
), 306
(2001
).59.
D.
Van der Spoel
, E.
Lindahl
, B.
Hess
, G.
Groenhof
, A. E.
Mark
, and H. J. C.
Berendsen
, J. Comput. Chem.
26
(16
), 1701
(2005
).60.
B.
Hess
, C.
Kutzner
, D.
van der Spoel
, and E.
Lindahl
, J. Chem. Theory Comput.
4
(3
), 435
(2008
).61.
W. L.
Jorgensen
, J.
Chandrasekhar
, J. D.
Madura
, R. W.
Impey
, and M. L.
Klein
, J. Chem. Phys.
79
(2
), 926
(1983
).62.
K.
Lindorff-Larsen
, S.
Piana
, K.
Palmo
, P.
Maragakis
, J. L.
Klepeis
, R. O.
Dror
, and D. E.
Shaw
, Proteins
78
(8
), 1950
(2010
).63.
J. K.
Noel
, M.
Levi
, M.
Raghunathan
, H.
Lammert
, R. L.
Hayes
, J. N.
Onuchic
, and P. C.
Whitford
, PLoS Comput. Biol.
12
(3
), e1004794
(2016
).© 2018 Author(s).
2018
Author(s)
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