The present work outlines a new method for treatment of charge-dependent polarizability in semiempirical quantum models for use in combined quantum-mechanical/molecular mechanical simulations of biological reactions. The method addresses a major shortcoming in the performance of conventional semiempirical models for these simulations that is tied to the use of a localized minimal atomic-orbital basis set. The present approach has the advantages that it uses a density basis that retains a set of linear-response equations, does not increase the atomic-orbital basis, and avoids the problem of artificial charge transfer and scaling of the polarizability seen in related models that allow atomic charges to fluctuate. The model introduces four new atom-based parameters and has been tested with the modified neglect of differential overlap d-orbital Hamiltonian against 1132molecules and ions and shown to decrease the dipole moment and polarizability errors by factors of 2 and 10, respectively, with respect to density-functional results. The method performs impressively for a variety of charge states (from 2+ to 2), and offers a potentially powerful extension in the design of next generation semiempirical quantum models for accurate simulations of highly charged biological reactions.

1.
W.
Thiel
, in
Advances in Chemical Physics
, edited by
I.
Prigogine
and
S. A.
Rice
(
Wiley
, New York,
1996
), Vol.
93
, pp.
703
757
.
2.
T.
Clark
,
J. Mol. Struct.: THEOCHEM
530
,
1
(
2000
).
3.
W.
Thiel
, in
Handbook of Molecular Physics and Quantum Chemistry
, edited by
S.
Wilson
(
Wiley
, Chichester,
2003
), Vol.
2
, pp.
487
502
.
4.
T.
Bredow
and
K.
Jug
,
Theor. Chem. Acc.
113
,
1
(
2005
).
5.
A.
Warshel
and
M.
Levitt
,
J. Mol. Biol.
103
,
227
(
1976
).
6.
M.
Garcia-Viloca
,
D. G.
Truhlar
, and
J.
Gao
,
J. Mol. Biol.
327
,
549
(
2003
).
7.
J.
Khandogin
,
K.
Musier-Forsyth
, and
D. M.
York
,
J. Mol. Biol.
330
,
993
(
2003
).
8.
J.
Khandogin
and
D. M.
York
,
Proteins
56
,
724
(
2004
).
9.
B. A.
Gregersen
,
X.
Lopez
, and
D. M.
York
,
J. Am. Chem. Soc.
125
,
7178
(
2003
).
10.
B. A.
Gregersen
,
X.
Lopez
, and
D. M.
York
,
J. Am. Chem. Soc.
126
,
7504
(
2004
).
11.
P.
Winget
,
C.
Selçuki
,
A.
Horn
,
B.
Martin
, and
T.
Clark
,
Theor. Chem. Acc.
110
,
254
(
2003
).
12.
M. I.
Bernal-Uruchurtu
,
M. T. C.
Martins-Costa
, and
M. F. R.-L. C.
Millot
,
J. Comput. Chem.
21
,
572
(
2000
).
13.
M.
Kolb
and
W.
Thiel
,
J. Comput. Chem.
14
,
775
(
1993
).
14.
W.
Weber
and
W.
Thiel
,
Theor. Chem. Acc.
103
,
495
(
2000
).
15.
M.
Bernal-Uruchurtu
and
M.
Ruiz-López
,
Chem. Phys. Lett.
330
,
118
(
2000
).
16.
T. J.
Giese
,
E. C.
Sherer
,
C. J.
Cramer
, and
D. M.
York
,
J. Chem. Theory Comput.
(in press).
17.
M.
Elstner
,
T.
Frauenheim
,
E.
Kaxiras
,
G.
Seifert
, and
S.
Suhai
,
Phys. Status Solidi B
217
,
357
(
2000
).
18.
M.
Elstner
,
Q.
Cui
,
P.
Munih
,
E.
Kaxiras
,
T.
Frauenheim
, and
M.
Karplus
,
J. Comput. Chem.
24
,
565
(
2003
).
19.
A.
Warshel
,
Computer Modeling of Chemical Reactions in Enzymes and Solutions
(
Wiley
, New York,
1991
).
20.
A.
Warshel
,
Acc. Chem. Res.
35
,
385
(
2002
).
21.
M.
Garcia-Viloca
,
J.
Gao
,
M.
Karplus
, and
D. G.
Truhlar
,
Science
303
,
186
(
2004
).
22.
W. A.
Parkinson
and
M. C.
Zerner
,
J. Chem. Phys.
94
,
478
(
1991
).
23.
M.
Dewar
,
Y.
Yamaguchi
, and
S.
Suck
,
Chem. Phys. Lett.
59
,
541
(
1974
).
24.
N.
Matsuzawa
and
D. A.
Dixon
,
J. Phys. Chem.
96
,
6232
(
1992
).
25.
G.
Schürer
,
P.
Gedeck
,
M.
Gottschalk
, and
T.
Clark
,
Int. J. Quantum Chem.
75
,
17
(
1999
).
26.
B.
Martin
,
P.
Gedeck
, and
T.
Clark
,
Int. J. Quantum Chem.
77
,
473
(
2000
).
27.
D.
Rinaldi
and
J.
Rivail
,
Theor. Chim. Acta
32
,
57
(
1974
).
28.
J. L.
Rivail
and
A.
Cartier
,
Mol. Phys.
36
,
1085
(
1978
).
29.
D.
Rinaldi
and
J.
Rivail
,
Theor. Chim. Acta
32
,
243
(
1974
).
30.
D. M.
York
and
W.
Yang
,
J. Chem. Phys.
104
,
159
(
1996
).
31.
W. J.
Mortier
,
K.
Van Genechten
, and
J.
Gasteiger
,
J. Am. Chem. Soc.
107
,
829
(
1985
).
32.
R. F.
Nalewajski
,
J. Phys. Chem.
89
,
2831
(
1985
).
33.
A. K.
Rappe
and
W. A.
Goddard
 III
,
J. Phys. Chem.
95
,
3358
(
1991
).
34.
S. W.
Rick
,
S. J.
Stuart
, and
B. J.
Berne
,
J. Chem. Phys.
101
,
6141
(
1994
).
35.
J.
Morales
and
T. J.
Martínez
,
J. Phys. Chem. A
105
,
2842
(
2001
).
36.
R.
Chelli
,
M.
Pagliai
,
P.
Procacci
,
G.
Cardini
, and
V.
Schettino
,
J. Chem. Phys.
122
,
074504
(
2005
).
37.
J.
Morales
and
T. J.
Martínez
,
J. Phys. Chem. A
108
,
3076
(
2004
).
38.
S. M.
Valone
and
S. R.
Atlas
,
J. Chem. Phys.
120
,
7262
(
2004
).
39.
J.
Cioslowski
and
B. B.
Stefanov
,
J. Chem. Phys.
99
,
5151
(
1993
).
40.
T. J.
Giese
and
D. M.
York
,
J. Chem. Phys.
120
,
7939
(
2004
).
41.
T. J.
Giese
,
B.
Gregersen
,
J.
Khandogin
,
Y.
Liu
,
E.
Mayaan
,
A.
Moser
,
K.
Nam
,
K.
Range
, and
D. M.
York
, http://riesling.chem.umn.edu/QCRNA
42.
K.
Range
,
M. J.
McGrath
,
X.
Lopez
, and
D. M.
York
,
J. Am. Chem. Soc.
126
,
1654
(
2004
).
43.
E.
Mayaan
,
K.
Range
, and
D. M.
York
,
JBIC, J. Biol. Inorg. Chem.
9
,
807
(
2004
).
44.
C. S.
López
,
O. N.
Faza
,
B. A.
Gregersen
,
X.
Lopez
,
A. R.
de Lera
, and
D. M.
York
,
ChemPhysChem
5
,
1045
(
2004
).
45.
C. S.
López
,
O. N.
Faza
,
A. R.
de Lera
, and
D. M.
York
,
Chem.-Eur. J.
11
,
2081
(
2005
).
46.
Y.
Liu
,
X.
Lopez
, and
D. M.
York
,
Chem. Commun. (Cambridge)
31
,
3909
(
2005
).
47.
A. D.
Becke
,
J. Chem. Phys.
98
,
5648
(
1993
).
48.
C.
Lee
,
W.
Yang
, and
R. G.
Parr
,
Phys. Rev. B
37
,
785
(
1988
).
49.
W.
Thiel
and
A. A.
Voityuk
,
Theor. Chim. Acta
81
,
391
(
1992
).
50.
W.
Thiel
and
A. A.
Voityuk
,
J. Phys. Chem.
100
,
616
(
1996
).
51.
J.
Khandogin
,
B. A.
Gregersen
,
W.
Thiel
, and
D. M.
York
,
J. Phys. Chem. B
109
,
9799
(
2005
).
52.
B. A.
Gregersen
,
J.
Khandogin
,
W.
Thiel
, and
D. M.
York
,
J. Phys. Chem. B
109
,
9810
(
2005
).
53.
W.
Thiel
, Program MNDO97 (
University of Zurich
, Zurich, Switzerland,
1998
).
54.
D.
Goldberg
,
Genetic Algorithms in Search, Optimization and Machine Learning
(
Addison-Wesley
, Reading, MA,
1989
).
55.
D. A.
Coley
,
An Introduction to Genetic Algorithms for Scientists and Engineers
(
World Scientific
, Singapore,
1999
).
56.
W. H.
Press
,
S. A.
Teukolsky
,
W. T.
Vetterling
, and
W. P.
Flannery
,
Numerical Recipes in Fortran
, 2nd ed. (
Cambridge University Press
, Cambridge,
1992
).
57.
I.
Rossi
and
D. G.
Truhlar
,
Chem. Phys. Lett.
233
,
231
(
1995
).
58.
T. R.
Cundari
,
J.
Deng
, and
W.
Fu
,
Int. J. Quantum Chem.
77
,
421
(
2000
).
59.
A. A.
Voityuk
and
N.
Rösch
,
J. Phys. Chem. A
104
,
4089
(
2000
).
60.
M. C.
Hutter
,
J. R.
Reimers
, and
N. S.
Hush
,
J. Phys. Chem. B
102
,
8080
(
1998
).
61.
See EPAPS Document No. E-JCPSA6-123-316538 for further discussion. This document can be reached via a direct link in the online article’s HTML reference section or via the EPAPS homepage (http://www.aip.org/pubservs/epaps.html).
62.
J. J. P.
Stewart
,
J. Comput. Chem.
10
,
209
(
1989
).
63.
M. J. S.
Dewar
,
E.
Zoebisch
,
E. F.
Healy
, and
J. J. P.
Stewart
,
J. Am. Chem. Soc.
107
,
3902
(
1985
).
64.
M. J.
Dewar
and
W.
Thiel
,
J. Am. Chem. Soc.
99
,
4899
(
1977
).
65.
D.
Bakowies
and
W.
Thiel
,
J. Comput. Chem.
17
,
87
(
1996
).
66.
V. J.
Docherty
,
D.
Pugh
, and
J. O.
Morley
,
J. Chem. Soc., Faraday Trans. 2
81
,
1179
(
1985
).
67.
J. O.
Morley
,
V. J.
Docherty
, and
D.
Pugh
,
J. Chem. Soc., Perkin Trans. 2
1987
,
1361
.
68.
M. G.
Papadopoulos
,
J.
Waite
, and
C. A.
Nicolaides
,
J. Chem. Phys.
77
,
2527
(
1982
).
69.
J.
Waite
,
M. G.
Papadopoulos
, and
C. A.
Nicolaides
,
J. Chem. Phys.
77
,
2536
(
1982
).
70.
J.
Waite
and
M. G.
Papadopoulos
,
J. Chem. Phys.
82
,
1427
(
1985
).
71.
CRC Handbook of Chemistry and Physics
, 83rd ed., edited by
D. R.
Lide
(
CRC
, Boca Raton, FL,
2003
).

Supplementary Material

You do not currently have access to this content.