174 COMPUTER HARDWARE, SOFTWARE
diverse “ training set ” of parameters),^37 and MNDO (the oldest method using
fewer parameters and slightly different functional forms).^38 A newer MNDO/d
method includesd - type functions for second - row and heavier main - group ele-
ments (much like the 3 - 21G( * ) basis set for second - row and heavier main -
group elements vs. 3 - 21G for fi rst - row elements).^39 A newer PM3(tm)^40
describes transition metals in terms of a minimal valence basis set [ nd , ( n + 1) s ,
(n + 1) p , where n is the principal quantum number]. PM3(tm) is normally used
in conjunction with PM3. Semiempirical calculations on molecules containing
up to 200 atoms are practical.
One example of the use of semiempirical methodology is provided in an
article detailing a molecular - dynamics simulation of the beta domain of
metallothionein with a semiempirical treatment of the metal core.^41 The beta
domain of rat liver metallothionein - 2 contains three - metal centers. In this
study, three molecular variants with different metal contents — (1) three
cadmium ions, (2) three zinc ions, and (3) one cadmium ion and two zinc
ions — were investigated using a conventional molecular dynamics simulation,
as well as a simulation with a semiempirical quantum - chemical description
(MNDO and MNDO/d) of the metal core embedded in a classical environ-
ment. For the purely classical simulations, the standard GROMOS96 force -
fi eld parameters were used, and parameters were estimated for cadmium. The
results of both kinds of simulations were compared to each other and to the
corresponding experimental X - ray crystallographic and NMR solution data.
The purely classical simulations were found to produce a too compact metal
cluster with partially incorrect geometries, which affected the enfolding protein
backbone structure. The inclusion of MNDO/d for the treatment of the metal
cluster improved the results to give correct cluster geometries and an overall
protein structure in agreement with experimental results. The metal cluster
and the cysteine residues bound to it were found to be structurally stable, while
the irregular polypeptide backbone loops between the cysteines exhibited a
considerable fl exibility. MNDO without extension to d orbitals failed to main-
tain the structure of the metal core.
4.5 Computer Software for Chemistry,
This section provides a snapshot of chemistry software and websites, arranged
alphabetically, available in early 2007. Any software listing will necessarily be
incomplete and out - of - date before this text ’ s publication. The emphasis in the
following listing is on software that contains algorithms suitable for use with
transition metals and biomolecules. More sophisticated software programs
allowing quantum mechanical (ab initio or density functional theory calcula-
tions) may require workstation - level computer hardware, although require-
ments change frequently as desktop and laptop machines become more
powerful. At the current time, most software suppliers offer very capable