The keyword `MOZYME` replaces the standard SCF procedure with a
localized molecular orbital (LMO) method. MOZYME was developed to allow
very large organic compounds, specifically enzymes, to be easily calculated. The
time required for a SCF calculation increases approximately linearly with the
size of the system, see literature on MOZYME
and Modeling proteins. MOZYME jobs do
not run faster when a GPU chip is used.

Although a job that uses the MOZYME technique should give results that are
the same as conventional SCF calculations, in practice there are differences.
Most of these differences are small, but in some jobs the differences between
MOZYME and conventional SCF calculations, particularly the calculation of
ΔH_{f}, can be significant. A single point
calculation using MOZYME and conventional methods would produce essentially the
same ΔH_{f}, and for the purposes of this
discussion the results of a single SCF calculated by both methods can be
regarded as being identical. The problem with different
ΔH_{f} occurs when multiple SCF calculations
are performed, this is the situation in a geometry optimization or reaction path
calculation. In such calculations, the LMOs that result from an SCF
calculation are used as starting LMOs in the next SCF calculation. In the
first SCF calculation, the starting LMOs are exact - they form rigorously
orthonormal sets, one for the occupied and one for the virtual sets. At the end of the SCF, small errors arising from truncation of the LMOs and
incomplete pairwise rotations give rise to a small degradation of the
orthonormal nature of the LMOs. In a single SCF, this degradation is
unimportant, but when many SCF calculations are done, the loss of orthonormality
increases steadily. This manifests itself as an error in the calculated
ΔH_{f} and to a much smaller extent in the
gradients, and therefore, by implication, in the geometry. The loss of orthonormality
could be corrected by re-orthogonalizing the LMOs, but the CPU cost of this is
great, and re-othogonalization is not done by default, although it can
be done if desired using `REORTHOG`. Fortunately, a very simple
procedure exists to completely correct this error: After any long run
involving many MOZYME SCF calculations, use the final geometry generated as the
starting point for a 1SCF calculation, and then use the ΔH_{f}
from that calculation. This strategy should be used:

(A) In global optimizations.

(B) In transition state location runs.

(C) At the end of IRC runs.

Do not use `OLDENS` as that would re-use the
now-inaccurate sets of LMOs, and thus defeat the purpose of doing the 1SCF
calculation. As mentioned above, the errors in the gradient are small, so
the geometry is essentially unaffected by the loss of orthonormality.
However, it is still a good practice to optimize geometries in three or more
separate runs, if only to provide an opportunity to check that the calculation
is proceeding as intended.

During geometry optimizations, the error in
ΔH_{f} caused by the deterioration of the
LMOs can result in the energy rising near the end of the run. If this
happens, the lowest energy structure will be output, instead of the last
structure calculated.

By default, the M.O.s printed are LMOs. If canonical M.O.s are needed,
use keyword `EIGEN`. EIGEN uses a large amount of
memory and might not work if the system is too large. Even if it does
work, it might take a lot of CPU time, so `EIGEN` should only be used with `
1SCF`.

With 1Gb of RAM, systems of up to 10,000 atoms can be run without paging. Above about 11,000 atoms, paging becomes severe, and jobs take longer than necessary. With 2Gb of RAM, systems of up to 18,500 atoms can be run without significant paging. A system of 36,774 atoms ran successfully using 8.2Gb of memory, but each geometry optimization cycle took about two hours.

If polarizabilities are required, use `
STATIC`. If keyword

The total charge on the system must be correct. If itÂ’s not, the charge will be changed to that predicted by the
Lewis structure. To prevent the charge being changed, use
`CHARGE=n`, even in cases where the system is neutral,
i.e., `CHARGE=0`. If `CHARGE=n`
is present, then any mistake made by MOZYME will be trapped and reported as soon
as the job starts. If `CHARGE=n` is not present, then the charge predicted by
the Lewis structure will be used.

- Only closed shell RHF calculations are allowed. This means that
`MOZYME`calculations are limited to species in their ground state. Radicals and electronic excited states cannot be run. Ions that are definitely open-shell, such as Cr(III), cannot be run. Only pre-set oxidation states are allowed, e.g. C^{IV}and Au^{I}. Oxidation states of metals can be changed using the`METAL`keyword, e.g.`METAL=(Au(+3))`. - The results are not so precise, so for runs that need high precision (such
as
`FORCE`calculations),`MOZYME`is discouraged. For proteins in particular, use a larger gradient norm criterion, e.g.`GNORM=5`, this will reduce the possibility of convergence failure. - For large systems, the recommended geometry optimizer is
`LBFGS`. This is a modified BFGS optimizer designed to minimize memory usage, and is the default for systems of 2000 parameters or more. If`LBFGS`is not wanted for any reason, then use`BFGS`, although it uses a lot more memory. The default optimizer,`EF`, uses a large amount of memory, and should therefore not be used in optimizing the geometry of large systems. In addition, because it uses a matrix inversion, it becomes very time consuming for large systems. - Electrostatic Potentials cannot be calculated, that is
__ESP____PMEP__

In some very specific cases, the MOZYME method can give rise to an incorrect
SCF, specifically the MOZYME SCF solution corresponds to an electronic excited state.
None of these cases ever occur in protein chemistry, unless severe errors are
made, but users should be aware of
their existence. The commonest incorrect SCF solutions are obtained
when the system should not be represented by a Lewis structure. A much
rarer type of error is found in some helical buckytubes when periodic boundary
conditions are imposed. In cases of this type, the Lewis structure
generator simply fails to make the correct Lewis structure, and instead attempts
to correct a faulty structure by assigning charges to two or more carbon
atoms. In all instances where incorrect SCF solutions are found, the
correct solution can be obtained by the appropriate use of `
CVB` or `SETPI.`

`MOZYME` can be used for simple geometric calculations, such as
geometry optimization, transition state location, and intrinsic and dynamic reaction
coordinates, and for the calculation of polarizability. For these calculations,
`MOZYME` can be run as a "stand alone" calculation. If a partial geometry
optimization is run, then the use of keyword `RAPID` should be
considered.

For calculation of vibrational frequencies, frequency-dependent
polarizability, and electronic excited states, `MOZYME` should be
run first, to optimize the geometry, then a conventional `MOPAC`
calculation run.

Another effective strategy is to run a `MOZYME` job, followed by a `
MOPAC` job, using the `
OLDGEO`
feature. When geometry optimizations are being run, a `MOZYME` job can be
run for a time, then a `MOPAC` job run, using `
RESTART`. That
is, the `RESTART` function will work when a geometry optimization or
transition state location calculation is run, regardless of the method used in
generating the SCF.