A brief overview of the performance of Molecular Mechanics and quantum chemical models (including SemiEmpirical models, HartreeFock models, Density Functional models, MP2 models, and the T1 thermochemical recipe) with regard to the calculation of equilibrium and transitionstate geometries, conformations and reaction thermochemistry is provided below. This is based on an extensive series or comparisons presented in A Guide to Molecular Mechanics and Quantum Chemical Comparisons which accompanies Spartan and is available as a PDF file from our main help page.
G  good 
C  good with cautious application 
P  poor 
task  molecular mechanics 
semi empirical 
Hartree Fock 
density functional 
MP2  T1 

geometry (organic)  
geometry (metals)  
transitionstate geometry  
conformation  
thermochemistry (general)  
thermochemistry (isodesmic)  
cost  low > high 
HartreeFock models with basis sets larger than 631G* do not provide significantly improved descriptions of either equilibrium or transitionstate geometries over the HartreeFock 631G* model nor (in most cases) the HartreeFock 321G model. Note, however, that Density Functional models and MP2 models require (at the very least) basis sets which incorporate polarization functions.
HartreeFock models do not provide a reliable account of the geometries of compounds incorporating transition metals, but the PM3 and PM6 SemiEmpirical models and Density Functional models provide perform well for these systems. MP2 models provide good geometries for some transition metal systems, but very poor geometries for others.
SemiEmpirical models may in some cases be suitable for identifying conformational minima, and for determining the geometries of these minima, but they are not suitable at providing accurate relative conformer energies.
The MMFF molecular mechanics model provides a good account of conformational energy differences in organic compounds. Note, however, that most of the data used in the assessment were also used to parameterize MMFF. Caution is needed in the application of MMFF outside the original range of its parameterization.
MP2 and Density Functional models are needed to accurately account for the energetics of reactions where bonds are broken or formed and to properly describe absolute activation energies. HartreeFock models are not satisfactory for this purpose. HartreeFock models are satisfactory , however, in description of relative activation energies.
HartreeFock, Density Functional and MP2 models provide an excellent account of the energetics of isodesmic reactions.
SemiEmpirical models are unsatisfactory in their description of the energetics of all types of reactions, isodesmic processes included.
Molecular Mechanics models are restricted to the description of molecular equilibrium geometry and conformation. They are perhaps the only practical techniques for searching conformation space for any but the simplest molecules or for systems with more than a few degrees of conformational freedom.
SemiEmpirical models are particularly attractive for:MP2 and Density Functional models are needed for accurate descriptions of the thermochemistry of reactions which involve explicit bond making or breaking, and for calculation of absolute activation energies. Density Functional models also provide good descriptions of reactions which involve net bond making or breaking. In practice, MP2 models may only be applied to relatively small molecules, whereas Density Functional models are comparable in cost to HartreeFock models for molecules of moderate size and less costly for large molecules.
Density Functional models are particularly attractive for:
Relative computation times for camphor (C_{10}H_{16}O), morphine (C_{17}H_{19}NO_{2}) and triacetyldynemicin A (C_{36}H_{25}NO_{12}) for a variety of models are provided below: 



camphor^{a}

morphine^{b}

triacetyldynemicin A^{c}


model 
energy^{ }

geometry^{d}

energy^{ }

geometry^{e}

energy^{ }

geometry^{f}



MMFF 
too small 


PM3 
to measure

0.1


HF/321G 
1

5

1^{g}

12

1^{h}

40

HF/631G* 
7

30

8

110

7^{}

360^{}

HF/6311+G** 
42

180








EDF2/631G* 
12

57

10

140

5

160

EDF2/6311+G** 
60

290

50







B3LYP/631G* 
13

65

12

160

10

400

B3LYP/6311+G** 
85

370

76







MP2/631G* 
27

270

80

2000

320



MP2/6311+G** 
260



650





^{}



a) 131 basis functions for 321G, 197 basis functions for
631G* and 338 basis functions for 6311+G** 
The estimates for geometry optimizations assume a fixed number of steps (increasing
with molecule size). The required number may vary by as much as a factor of
two depending on the molecule and the "quality" of the guess. Transition
state optimizations will typically require two to three times the number of
optimization steps as equilibrium geometry optimizations. 