Biomedical Engineering Reference
In-Depth Information
Repeating the optimization from different starting points has identified many local minima
and the conformation corresponding to energy ε
1
appears to be the global minimum.
k
B
T
ε
1
Figure 6.3
Conformation search
Our MM calculations refer to the molecule at 0 K, whilst we would normally concern
ourselves with molecules at room temperature. At 0 K, we would find all molecules in
the lowest energy conformation but at other temperatures we will find certain fractions
of the molecules in higher energy conformations. These fractions are determined by the
Boltzmann factor
exp
ε
k
B
T
−
where
k
B
is the Boltzmann constant. I have therefore drawn a vertical line on the figure
of size
k
B
T
, and we see that the first four conformations lie close together (compared to
the yardstick
k
B
T
), and so we expect that all four would make a significant contribution to
measured properties of the molecule at temperature
T
.
The remaining groups of conformations are far away from the first four in terms of the
yardstick
k
B
T
, and so can be discarded.
Several approaches have been applied to the problem of automatically identifying the
low-energy conformations of a given molecule. Molecular flexibility is usually associated
with rotation of unhindered bond dihedral angles, with little change in bond lengths and
bond angles. A common theme is therefore to limit the exploration to those parameters that
have the
least
effect on the energy. Another strategy is to automatically scan a possible
structure for unfavourably close nonbonded atoms and unlikely ring closure bond lengths
before optimization.
A choice then has to be made to decide whether the starting structure should be the same
for every optimization, or each optimization should start with the structure found by the
