Parameterization of molecular mechanics potential functions

(Leach pgs. 228-231; Grant and Richards pgs 41-43)

 

·     Some methods for deriving atomic charges are mentioned above.

 

·     Other parameters (e.g. force constants and equilibrium values) can be chosen by trial and error, or by fitting (e.g. by a least-squares fit), to experimental data or ab initio calculation results.

 

·     Bond lengths and angles can be taken from gas-phase structural studies on small molecules (e.g. microwave spectra, or electron diffraction). Force constants can be found by fitting to experimental or calculated harmonic vibrational frequencies.

 

·     Barriers to rotation around torsion angles can be calculated at the ab initio level can be found from ab initio calculations on small molcules (recall that Hartree-Fock calculations can give useful results for conformational energy changes).

 

·     When fitting molecular mechanics torsion terms, it should be remembered that MM 1-4 non-bonded interactions will also contribute.

 

·     Non-bonded parameters (van der Waals and electrostatic) can be found from ab initio calculations, with the caveat that Hartree-Fock calculations do not include dispersion effects, so better calculations (e.g. MP2) would be required for a good fit. However, typically the van der Waals terms have little influence on structure, so are optimizeded in the final stages of fitting to improve the performance of the model.

 

Next: example of a MM topology