In earlier works, we showed that the entropic effect originating from the translational displacement of water molecules plays the pivotal role in protein folding and denaturation. The two different solvent models, hard-sphere solvent and model water, were employed in theoretical methods wherein the entropic effect was treated as an essential factor. However, there were similarities and differences in the results obtained from the two solvent models. In the present work, to unveil the physical origins of the similarities and differences, we simultaneously consider structural transition, cold denaturation, and pressure denaturation for the same protein by employing the two solvent models and considering three different thermodynamic states for each solvent model. The solvent-entropy change upon protein folding/unfolding is decomposed into the protein-solvent pair (PA) and many-body (MB) correlation components using the integral equation theories. Each component is further decomposed into the excluded-volume (EV) and solvent-accessible surface (SAS) terms by applying the morphometric approach. The four physically insightful constituents, (PA, EV), (PA, SAS), (MB, EV), and (MB, SAS), are thus obtained. Moreover, (MB, SAS) is discussed by dividing it into two factors. This all-inclusive investigation leads to the following results: (1) the protein-water many-body correlation always plays critical roles in a variety of folding/unfolding processes; (2) the hard-sphere solvent model fails when it does not correctly reproduce the protein-water many-body correlation; (3) the hard-sphere solvent model becomes problematic when the dependence of the many-body correlation on the solvent number density and temperature is essential: it is not quite suited to studies on cold and pressure denaturating of a protein; (4) when the temperature and solvent number density are limited to the ambient values, the hard-sphere solvent model is usually successful; and (5) even at the ambient values, however, the many-body correlation plays significant roles in the β-sheet formation and argument of relative stabilities of very similar structures of a protein. These results are argued in detail with respect to the four physically insightful constituents and the two factors mentioned above. The relevance to the absence or presence of hydrogen-bonding properties in the solvent is also discussed in detail.

1.
A.
Pastore
,
S. R.
Martin
,
A.
Politou
,
K. C.
Kondapalli
,
T.
Stemmler
, and
P. A.
Temussi
,
J. Am. Chem. Soc.
129
,
5374
(
2007
).
2.
P. L.
Privalov
,
Y. V.
Griko
, and
S. Y.
Venyaminov
,
J. Mol. Biol.
190
,
487
(
1986
).
3.
P. L.
Privalov
,
Pure Appl. Chem.
79
,
1445
(
2007
).
4.
C.
Cléry
,
F.
Renault
, and
P.
Masson
,
FEBS Lett.
370
,
212
(
1995
).
5.
F.
Meersman
,
C. M.
Dobson
, and
K.
Heremans
,
Chem. Soc. Rev.
35
,
908
(
2006
).
6.
R.
Kitahara
,
S.
Yokoyama
, and
K.
Akasaka
,
J. Mol. Biol.
347
,
277
(
2005
).
7.
J. F.
Back
,
D.
Oakenfull
, and
M. B.
Smith
,
Biochemistry
18
,
5191
(
1979
).
8.
K.
Gekko
and
S.
Koga
,
J. Biochem.
94
,
199
(
1983
).
9.
N. K.
Poddar
,
Z. A.
Ansari
,
R. K. B.
Singh
,
A. A.
Moosavi-Movahedi
, and
F.
Ahmad
,
Biophys. Chem.
138
,
120
(
2008
).
10.
H. S.
Frank
and
M. W.
Evans
,
J. Chem. Phys.
13
,
507
(
1945
).
11.
P.
De Los Rios
and
G.
Caldarelli
,
Phys. Rev. E
62
,
8449
(
2000
).
12.
C. L.
Dias
,
T.
Ala-Nissila
,
M.
Karttunen
,
I.
Vattulainen
, and
M.
Grant
,
Phys. Rev. Lett.
100
,
118101
(
2008
).
13.
G.
Graziano
,
Phys. Chem. Chem. Phys.
12
,
14245
(
2010
).
14.
T.
Yoshidome
and
M.
Kinoshita
,
Phys. Rev. E
79
,
030905(R)
(
2009
).
15.
H.
Oshima
,
T.
Yoshidome
,
K.
Amano
, and
M.
Kinoshita
,
J. Chem. Phys.
131
,
205102
(
2009
).
16.
T.
Yoshidome
and
M.
Kinoshita
,
Phys. Chem. Chem. Phys.
14
,
14554
(
2012
).
17.
S. V.
Buldyrev
,
P.
Kumar
,
S.
Sastry
,
H. E.
Stanley
, and
S.
Weiner
,
J. Phys.: Condens. Matter
22
,
284109
(
2010
).
18.
A.
Paliwal
,
D.
Asthagiri
,
D. P.
Bossev
, and
M. E.
Paulaitis
,
Biophys. J.
87
,
3479
(
2004
).
19.
B.
Wroblowski
,
J. F.
Díaz
,
K.
Heremans
, and
Y.
Engelborghs
,
Proteins
25
,
446
(
1996
).
20.
D.
Paschek
and
A. E.
García
,
Phys. Rev. Lett.
93
,
238105
(
2004
).
21.
Y.
Harano
and
M.
Kinoshita
,
J. Phys.: Condens. Matter
18
,
L107
(
2006
).
22.
Y.
Harano
and
M.
Kinoshita
,
J. Chem. Phys.
125
,
024910
(
2006
).
23.
Y.
Harano
,
T.
Yoshidome
, and
M.
Kinoshita
,
J. Chem. Phys.
129
,
145103
(
2008
).
24.
T.
Yoshidome
,
Y.
Harano
, and
M.
Kinoshita
,
Phys. Rev. E
79
,
011912
(
2009
).
25.
J. R.
Grigera
and
A. N.
McCarthy
,
Biophys. J.
98
,
1626
(
2010
).
26.
R.
Sarma
and
S.
Paul
,
J. Chem. Phys.
136
,
114510
(
2012
).
27.
G.
Graziano
,
Int. J. Biol. Macromol.
50
,
230
(
2012
).
28.
T. F.
O’Connor
,
P. G.
Debenedetti
, and
J. D.
Carbeck
,
Biophys. Chem.
127
,
51
(
2007
).
29.
A. J.
Saunders
,
P. R.
Davis-Searles
,
D. L.
Allen
,
G. J.
Pielak
, and
D. A.
Erie
,
Biopolymers
53
,
293
(
2000
).
30.
H.
Oshima
and
M.
Kinoshita
,
J. Chem. Phys.
138
,
245101
(
2013
).
31.
A.
Lerbret
,
P.
Bordat
,
F.
Affouard
,
A.
Hédoux
,
Y.
Guinet
, and
M.
Descamps
,
J. Phys. Chem. B
111
,
9410
(
2007
).
32.
F.-F.
Liu
,
L.
Ji
,
L.
Zhang
,
X.-Y.
Dong
, and
Y.
Sun
,
J. Chem. Phys.
132
,
225103
(
2010
).
33.
T.
Yoshidome
,
M.
Kinoshita
,
S.
Hirota
,
N.
Baden
, and
M.
Terazima
,
J. Chem. Phys.
128
,
225104
(
2008
).
34.
T.
Lazaridis
and
M.
Karplus
,
J. Chem. Phys.
105
,
4294
(
1996
).
35.
P. G.
Kusalik
and
G. N.
Patey
,
J. Chem. Phys.
88
,
7715
(
1988
).
36.
P. G.
Kusalik
and
G. N.
Patey
,
Mol. Phys.
65
,
1105
(
1988
).
37.
S.
Yasuda
,
H.
Oshima
, and
M.
Kinoshita
,
J. Chem. Phys.
137
,
135103
(
2012
).
38.
M.
Kinoshita
and
D. R.
Bérard
,
J. Comput. Phys.
124
,
230
(
1996
).
39.
N. M.
Cann
and
G. N.
Patey
,
J. Chem. Phys.
106
,
8165
(
1997
).
40.
M.
Kinoshita
,
J. Chem. Phys.
128
,
024507
(
2008
).
41.
J.-P.
Hansen
and
I. R.
McDonald
,
Theory of Simple Liquids
, 3rd ed. (
Academic
,
London
,
2006
).
42.
R.
Roth
,
Y.
Harano
, and
M.
Kinoshita
,
Phys. Rev. Lett.
97
,
078101
(
2006
).
43.
P.-M.
König
,
R.
Roth
, and
K. R.
Mecke
,
Phys. Rev. Lett.
93
,
160601
(
2004
).
44.
CRC Handbook of Chemistry and Physics
, 94th ed., edited by
W. M.
Haynes
(
CRC Press
,
Boca Raton
,
2013
).
45.
M.
Kinoshita
,
Y.
Harano
, and
R.
Akiyama
,
J. Chem. Phys.
125
,
244504
(
2006
).
46.
T.
Imai
,
Y.
Harano
,
M.
Kinoshita
,
A.
Kovalenko
, and
F.
Hirata
,
J. Chem. Phys.
126
,
225102
(
2007
).
47.
B. R.
Brooks
,
R. E.
Bruccoleri
,
B. D.
Olafson
,
D. J.
States
,
S.
Swaminathan
, and
M.
Karplus
,
J. Comput. Chem.
4
,
187
(
1983
).
48.
M.
Feig
,
J.
Karanicolas
, and
C. L.
Brooks
III
,
J. Mol. Graphics Modell.
22
,
377
(
2004
).
49.
T.
Imai
and
Y.
Sugita
,
J. Phys. Chem. B
114
,
2281
(
2010
).
50.
M.
Kinoshita
and
H.
Oshima
,
Chem. Phys. Lett.
610
,
1
(
2014
).
51.
T.
Imai
,
Y.
Harano
,
M.
Kinoshita
,
A.
Kovalenko
, and
F.
Hirata
,
J. Chem. Phys.
125
,
024911
(
2006
).
52.
A. D.
MacKerell
, Jr.
,
D.
Bashford
,
M.
Bellott
,
R. L.
Dunbrack
, Jr.
,
J. D.
Evanseck
,
M. J.
Field
,
S.
Fischer
,
J.
Gao
,
H.
Guo
,
S.
Ha
,
D.
Joseph-McCarthy
,
L.
Kuchnir
,
K.
Kuczera
,
F. T. K.
Lau
,
C.
Mattos
,
S.
Michnick
,
T.
Ngo
,
D. T.
Nguyen
,
B.
Prodhom
,
W. E.
Reiher
III
,
B.
Roux
,
M.
Schlenkrich
,
J. C.
Smith
,
R.
Stote
,
J.
Straub
,
M.
Watanabe
,
J.
Wiórkiewicz-Kuczera
,
D.
Yin
, and
M.
Karplus
,
J. Phys. Chem. B
102
,
3586
(
1998
).
53.
T.
Morita
,
Prog. Theor. Phys.
23
,
829
(
1960
).
54.
T.
Morita
and
K.
Hiroike
,
Prog. Theor. Phys.
25
,
537
(
1961
).
55.
S.
Asakura
and
F.
Oosawa
,
J. Chem. Phys.
22
,
1255
(
1954
).
56.
S.
Asakura
and
F.
Oosawa
,
J. Polym. Sci.
33
,
183
(
1958
).
57.
H. S.
Ashbaugh
and
M. E.
Paulaitis
,
J. Phys. Chem.
100
,
1900
(
1996
).
58.
M. L.
Connolly
,
J. Appl. Crystallogr.
16
,
548
(
1983
).
59.
M. L.
Connolly
,
J. Am. Chem. Soc.
107
,
1118
(
1985
).
61.
A. P.
Willard
and
D.
Chandler
,
J. Chem. Phys.
141
,
18C519
(
2014
).
62.
Y.
Li
,
B.
Shan
, and
D. P.
Raleigh
,
J. Mol. Biol.
368
,
256
(
2007
).
63.
M.
Aznauryan
,
D.
Nettels
,
A.
Holla
,
H.
Hofmann
, and
B.
Schuler
,
J. Am. Chem. Soc.
135
,
14040
(
2013
).
64.
K.
Oda
,
R.
Kodama
,
T.
Yoshidome
,
M.
Yamanaka
,
Y.
Sambongi
, and
M.
Kinoshita
,
J. Chem. Phys.
134
,
025101
(
2011
).
65.
T.
Ikkai
and
T.
Ooi
,
Biochemistry
5
,
1551
(
1966
).
66.
P. S.
Niranjan
,
P. B.
Yim
,
J. G.
Forbes
,
S. C.
Greer
,
J.
Dudowicz
,
K. F.
Freed
, and
J. F.
Douglas
,
J. Chem. Phys.
119
,
4070
(
2003
).
67.
D.
Foguel
,
M. C.
Suarez
,
A. D.
Ferrão-Gonzales
,
T. C. R.
Porto
,
L.
Palmieri
,
C. M.
Einsiedler
,
L. R.
Andrade
,
H. A.
Lashuel
,
P. T.
Lansbury
,
J. W.
Kelly
, and
J. L.
Silva
,
Proc. Natl. Acad. Sci. U. S. A.
100
,
9831
(
2003
).
68.
C. F. S.
Bonafe
,
C. M. R.
Vital
,
R. C. B.
Telles
,
M. C.
Gonçalves
,
M. S. A.
Matsuura
,
F. B. T.
Pessine
,
D. R. C.
Freitas
, and
J.
Vega
,
Biochemistry
37
,
11097
(
1998
).
69.
R.
Mishra
and
R.
Winter
,
Angew. Chem., Int. Ed.
47
,
6518
(
2008
).
70.
S.
Highsmith
,
Arch. Biochem. Biophys.
180
,
404
(
1977
).
71.
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