We introduce a straightforward, single-ensemble, path sampling approach to calculate free energy differences based on Jarzynski’s relation. For a two-dimensional “toy” test system, the new (minimally optimized) method performs roughly one hundred times faster than either optimized “traditional” Jarzynski calculations or conventional thermodynamic integration. The simplicity of the underlying formalism suggests the approach will find broad applicability in molecular systems.

1.
D. M.
Zuckerman
and
T. B.
Woolf
,
Phys. Rev. Lett.
89
,
180602
(
2002
).
2.
J.
Liphardt
,
S.
Dumont
,
S. B.
Smith
,
I.
Tinoco
, and
C.
Bustamante
,
Science
296
,
1832
(
2002
).
3.
S. X.
Sun
,
J. Chem. Phys.
118
,
5769
(
2003
).
4.
C.
Jarzynski
,
Phys. Rev. Lett.
78
,
2690
(
1997
).
5.
C.
Oostenbrink
and
W. F.
van Gunsteren
,
J. Comput. Chem.
24
,
1730
(
2003
).
6.
T. Z.
Mordasini
and
J. A.
McCammon
,
J. Phys. Chem.
104
,
360
(
2000
).
7.
G.
Hummer
,
J. Chem. Phys.
114
,
7330
(
2001
).
8.
S.
Park
,
F.
Khalili-Araghi
,
E.
Tajkhorshid
, and
K.
Schulten
,
J. Chem. Phys.
119
,
3559
(
2003
).
9.
M. R.
Shirts
,
J. W.
Pitera
,
W. C.
Swope
, and
V. S.
Pande
,
J. Chem. Phys.
119
,
5740
(
2003
).
10.
A. R. Leach, Molecular Modelling Principles and Applications (Prentice Hall, Dorset, 2001), 2nd ed.
11.
C. Sotriffer, G. Klebe, M. Stahl, and H.-J. Bohm, Burger’s Medicinal Chemistry and Drug Discovery, Vol. 1 (Wiley, New York, 2003), 6th ed.
12.
G. E.
Crooks
,
Phys. Rev. E
61
,
2361
(
2000
).
13.
C.
Jarzynski
,
Phys. Rev. E
65
,
046122
(
2002
).
14.
R.
Bitetti-Putzer
,
W.
Yang
, and
M.
Karplus
,
Chem. Phys. Lett.
377
,
633
(
2003
).
15.
F. M. Ytreberg and D. M. Zuckerman (unpublished).
16.
D. M.
Zuckerman
and
T. B.
Woolf
,
Chem. Phys. Lett.
351
,
445
(
2002
).
17.
L. R.
Pratt
,
J. Phys. Chem.
85
,
5045
(
1986
).
18.
P. G.
Bolhuis
,
D.
Chandler
,
C.
Dellago
, and
P. L.
Geissler
,
Annu. Rev. Phys. Chem.
53
,
291
(
2002
).
19.
C.
Dellago
,
P. G.
Bolhuis
,
F. S.
Csajka
, and
D.
Chandler
,
J. Chem. Phys.
108
,
1964
(
1998
).
20.
G. E.
Crooks
and
D.
Chandler
,
Phys. Rev. E
64
,
026109
(
2001
).
21.
D. M.
Zuckerman
and
T. B.
Woolf
,
J. Chem. Phys.
111
,
9475
(
1999
).
22.
D. Frenkel and B. Smit, Understanding Molecular Simulation (Academic, San Diego, 1996).
23.
W.
Yang
,
R.
Bitetti-Putzer
, and
M.
Karplus
,
J. Chem. Phys.
120
,
2618
(
2004
).
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