One important limitation of current
molecular mechanics methods is that the electrostatic properties cannot change
in response to changes in the molecular environment, structure or interactions
- the atomic charges are fixed and unchanging.
In reality, applying an electric field (e.g. due to surrounding molecules) will cause a change in the electronic distribution of a molecule - it will be polarized.
A dipole, m, will be induced, proportional to the induced field E:
m = aE
where a is the
polarizability.
·
One way to include polarizability effects is to allow induced
dipoles on every atom, by associating a polarizability with each atom, and
calculating the electric field at each atom. This incurs a considerable extra
computational expense (particularly because all the dipoles should be
calculated iteratively until they are self-consistent), but should provide a
better model.
·
Development of polarizable MM potential functions is a very active
area of current research - the next generation of organic/biomolecular
potential functions will include polarization.
The molecular mechanics potential
function given above calculates the electrostatic and van der Waals energies as
a sum of pairwise interactions, i.e.
by adding together the interaction energies of all pairs of atoms.
·
However, in reality, the interaction energy of e.g. three molecules
is not equal to the sum of the three separate interactions.
·
Many-body effects (due to the association of more than two
molecules) should be included. Polarization, as described above, is an example.
·
Accurate calculations show that 3-body interactions also contribute
to the dispersion energy, but this is a relatively small effect (e.g. 10% of
the lattice energy of crystalline argon).
·
More importantly, including many-body effects would significantly
increase the computer time required for a calculation - the calculation of
non-bonded interactions is the most demanding part of a MM calculation on a
large molecule, even with only pairwise interactions calculated (the number of
pair interactions to be calculated is N(N-1)/2, where N is the number of atoms,
e.g. 499500 interactions for a system of only 1000 atoms), and the introduction
of three-body interactions would increase the computational requirements
enormously.