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| Vcharge |
Download Vcharge |
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Vcharge provides fast,
easy access to accurate partial charges for virtually any drug-like
compound. It is thus valuable in a wide range of modeling and QSAR
applications.
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| Key strengths |
- Accuracy
"Ab initio-like" partial atomic charges accurately reproduce
electrostatic potentials from Hartree-Fock calculations at the 6-31G*
level (SBKJC core potentials for iodine). See section on Accuracy,
below.
- Broad applicability
The new VC/2004 parameter set allows charges to be computed for
virtually any stable compound composed of the elements hydrogen,
carbon, oxygen, nitrogen, phosphorous, sulfur, fluorine, chlorine,
bromine and iodine. Results do not depend upon molecular conformation
- Speed
Only about 0.1 second for a drug-like compound
- Convenience
Reads and writes SDfiles, and the free Vdisplay program allows
graphical review of the results. Both Linux and Windows versions are
available, and the Windows version of Vcharge includes a
straightforward graphical user interface
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following sections provide further details on Vcharge. |
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Accuracy and Range of
Applicability |
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VeraChem's latest parameter set,
VC/2004, includes new atom types and has been more thoroughly
optimized. It therefore is more broadly applicable and more accurate
than VC/2003.. |
The VC/2004 parameterization
yields partial charges that accurately reproduce Hartree-Fock 6-31G*
potentials at CHELPG sampling points. The potentials typically agree to
within an RMSD of ~4 kcal/mol-e. For comparison, VC/2003 parameters
gave an RMSD of ~5 kcal/mol-e for the same set of over 350 molecules. |
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Tests on molecules for which other charge sets
have been published indicate that Vcharge is as accurate, relative to
6-31G* potentials, as much slower methods, such as RESP and AM1/BCC and
is substantially more accurate than simpler approaches such as
Gasteiger-Marselli. (See References below.)
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VC/2004 charges are strikingly similar to those
in widely used force fields, such as AMBER and CHARMM22. Thus, for the
20 common amino acids, Vcharge matches CHARMM22 and AMBER94 with RMSDs
of only 0.07 e and 0.10 e, respectively, and with correlation
coefficients of 0.98 and 0.95. These differences are comparable to the
differences between CHARMM22 and AMBER94 themselves: RMSD 0.10,
correlation coefficient 0.90. Therefore, VC/2004 charges are compatible
with these force fields and are appropriate for ligands when a protein
is treated by the CHARMM22 or AMBER94 force fields.
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| Windows
User-Interface |
Included with the MS Windows version of Vcharge,
this convenient graphical user interface makes it particularly
straightforward to run Vcharge and view its results. The interface
brings together Vcharge, our molecular display program Vdisplay, and helpful Vcharge support
utilities, described in the following section.
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| Vcharge
Support Utilities |
| Two helpful utility programs are
provided with both the Linux and Windows versions of Vcharge: |
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extractMols makes it easy to check
and correct any molecules that may require special attention, and then
reprocess them with Vcharge. extractMols analyzes the output SDfile
from Vcharge and writes a short SDFile containing any molecules for
which charges were not computed.
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extractCharges simplifies viewing
of partial charges by reading the output SDfile from Vcharge and
writing a text file that lists the name of each molecule followed by
its atomic partial charges, one per line. |
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How Vcharge Works |
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Vchargeis an
electronegativity equalization method, where the electronegativity of
each atom depends upon its atomic number, hybridization, and bonding
environment within the molecule, and where special constraints are
applied to keep too much charge from flowing off ionized groups. The
constrained equalization problem is solved by an adaptation of the
method of Lagrangian multipliers.
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A unique feature of Vchargeis its
handling of alternate resonance forms. Alternate resonance forms of
each molecule are automatically identified, and the atomic
electronegativities and hardnesses are averaged over the resonance
forms. This ensures that equal charges are assigned to chemically
equivalent atoms, even when this equivalence is not apparent from the
single resonance form provided in the input SDfile. For example,
nitrogens N1 and N2 illustrated below would not be considered
equivalent if resonance forms were not considered. |
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| Ionization and tautomer states
are taken as specified in the input SDfile. |
Vcharge
version 1.0 for Linux and MS Windows 2000/XP.
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Vdisplay,
a convenient Windows viewer for Vcharge output, is available for free
download . |
REFERENCES |
| Main Citation |
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Fast assignment of accurate partial atomic
charges. An electronegativity equalization method that accounts for
alternate resonance forms. Gilson,M.K., Gilson,H.S.R. &
Potter,M.J.; J. Chem. Inf. Comput. Sci. 2003, 43(6), 1982-1997. |
Background Citations |
Identification
of
symmetries in molecules and complexes; Chen, W., Huang, J., &
Gilson, M.K.; J. Chem. Inf. Comput. Sci., 2004, 44, 1301-1313.
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Bayly, C. I.; Cieplak, P.; Cornell, W. D.;
Kollman, P.A.; J. Phys. Chem. 1993, 97, 10269-1028. |
Jakalian, A.; Bush, B. L.; Jack, D. B.;
Bayly, C. I;. J. Comput. Chem. 2000, 21, 132-146.
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Jakalian, A.; Jack, D. B.; Bayly, C. I.;
J. Comput. Chem. 2002, 23, 1623-1641
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Breneman, C. M.; Wiberg, K. B.; J. Comput.
Chem. 1990, 11, 361.
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Schmidt, M. W.; Baldridge, K. K.; Boatz,
J. A.; Elbert, S. T.; Gordon, M. S.; Jensen, J. H.; Koseki, S.;
Matsunaga, N.; Nguyen, K. A.; Su, S. J.; Windus, T. L.; Dupuis, M.;
Montgomery, J. A; J. Comp. Chem. 1993, 14, 1347-1363.
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Cornell, W.; Cieplak, P.; Bayly, C.;
Gould, I.; Merz,Jr., K.; Ferguson, D.; Spellmeyer, D.; Caldwell, T. F.
J.; P.A.,; Kollman; J. Am. Chem. Soc. 1995, 117, 5179-5197.
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| Molecular Simulations Inc. Waltham, MA.
CHARMm Version 22., 1992.. |
MacKerell, Jr., A. D.; Wiokiewicz-Kuczera,
J.; Karplus, M.; J. Am. Chem. Soc. 1995, 117, 11946-11975
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| Release
Notes |
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