A new method of simultaneously scaling and shifting the Lennard‐Jones (LJ) potential in molecular dynamics (MD) and thermodynamic integration (TI) simulations is presented. The approach allows the smooth creation or annihilation of atoms or molecules in an ensemble of solvent molecules during a molecular simulation. By scaling and shifting the LJ potential in the direction of the interatomic distance between particles, the method eliminates the problem of the creation or annihilation of a large repulsive LJ potential at the initial or final state of a TI. The optimal degree of shifting and scaling the LJ potential as a function of a control variable λ was studied for the annihilation and creation of neon in aqueous solution. The method was further tested on the calculation of the free energy of aqueous solvation of a small molecule, ethanol. In contrast to linear scaling of the LJ potential during TI, the calculated free energies using the new separation‐shifted scaling approach are reasonably well converged after 200–500 ps of simulation and show smaller hysteresis comparing forward and reverse TI.

1.
J. A. McCammon and S. C. Harvey, in Dynamics of Proteins and Nucleic Acids (Cambridge University, Cambridge, 1987).
2.
T. P.
Straatsma
and
J. A.
McCammon
,
Annu. Rev. Phys. Chem.
43
,
407
(
1992
).
3.
D. L.
Beveridge
and
F. M.
DiCapua
,
Annu. Rev. Biophys. Biophys. Chem.
18
,
431
(
1989
).
4.
A. J.
Cross
,
Chem. Phys. Lett.
128
,
198
(
1986
).
5.
M.
Mezei
and
D. L.
Beveridge
,
Ann. Acad. Sci.
482
,
1
(
1986
).
6.
M. R.
Mruzik
,
F. F.
Farid
,
F.
Abraham
,
P. E.
Schreiber
, and
G. M.
Pound
,
J. Chem. Phys.
64
,
481
(
1982
).
7.
D. A.
Pearlman
and
P. A.
Kollman
,
J. Chem. Phys.
91
,
7831
(
1989
).
8.
T. P.
Straatsma
,
H. J. C.
Berendsen
, and
J. P. M.
Postma
,
J. Chem. Phys.
85
,
6720
(
1986
).
9.
J. P. M.
Postma
,
H. J. C.
Berendsen
, and
J. R.
Haak
,
Faraday Symp. Chem. Soc.
17
,
55
(
1982
).
10.
D. A.
Pearlman
and
P. A.
Kollman
,
J. Chem. Phys.
94
,
4532
(
1990
).
11.
T. P.
Straatsma
,
M.
Zacharias
, and
J. A.
McCammon
,
Chem. Phys. Lett.
196
,
297
(
1992
).
12.
Y.
Sun
,
D.
Spellmeyer
,
D. A.
Pearlman
, and
P. A.
Kollman
,
J. Am. Chem. Soc.
114
,
6798
(
1992
).
13.
M.
Zacharias
,
T. P.
Straatsma
,
J. A.
McCammon
, and
F. A.
Quiocho
,
Biochem.
32
,
7428
(
1993
).
14.
P. R.
Gerber
,
A. E.
Mark
, and
W. F.
van Gunsteren
,
J. Comput. Aided Mol. Design
7
,
305
(
1993
).
15.
T. P.
Straatsma
and
J. A.
McCammon
,
J. Chem. Phys.
95
,
1175
(
1991
).
16.
W. F. van Gunsteren and H. J. C. Berendsen, Groningen Molecular Simulation (GROMOS) Library Manual, BIOMOS B.V., Nijenborgh 16, 9747 AG Groningen, The Netherlands.
17.
T. P.
Straatsma
and
J. A.
McCammon
,
J. Comput. Chem.
11
,
943
(
1990
).
18.
J. J.
Nicolas
,
K. E.
Gubbins
,
W. B.
Street
, and
D. J.
Tildesley
,
Mol. Phys.
37
,
1429
(
1979
).
19.
H. J. C.
Berendsen
,
J. R.
Grigera
, and
T. P.
Straatsma
,
J. Phys. Chem.
91
,
6269
(
1987
).
20.
H. J. C.
Berendsen
,
J. P. M.
Postma
,
W. F.
van Gunsteren
,
A.
DiNola
, and
J. R.
Haak
,
J. Chem. Phys.
81
,
3684
(
1984
).
21.
J.
Ryckaert
,
G.
Ciccotti
, and
H. J. C.
Berendsen
,
J. Comput. Phys.
23
,
327
(
1977
).
22.
F. Franks and D. S. Reid, in Water A Comprehensive Treatise, edited by F. Franks (Plenum, New York, 1973), p. 323.
23.
S.
Cabani
,
P.
Gianni
,
V.
Mollica
, and
L.
Lepori
,
J. Sol. Chem.
10
,
563
(
1981
).
24.
M.
Mezei
,
Molecular Simulations
2
,
201
(
1989
).
This content is only available via PDF.
You do not currently have access to this content.