many of our molecular modeling investigations the goal is to determine
the lowest-energy conformation of a molecule. The larger the molecule
is, the more difficult this becomes. The schematic potential energy surface
at right illustrates the concept. Large molecules have a large number
of possible conformations, many of which represent local minima on the
potential energy surface. The goal of the calculation is to find low-energy
minima including the global minimum. The first step in a MM calculation
is to obtain an initial molecular structure. Starting structures are often
built on the computer using the AMBER
software or another modeling program called HyperChem.
For large molecules it is useful to start with a known structure obtained
by some other method, such as X-ray crystallography. These structures
can often be obtained from the Protein
Data Bank, a collection of 3-D biological molecular structure data.
If the procedure used to sample the molecule's conformational space is
adequate, the results of the MM calculation should not depend on the choice
of starting structure. After obtaining an initial structure, the next
step is to optimize its geometry by minimizing its energy. The resulting
conformation corresponds to a local minimum on the potential energy surface.