Biomedical Engineering Reference
In-Depth Information
previous successful optimization. The latter choice is often favoured, on the grounds that
one low-energy conformation is pretty much like another, and starting from one successful
geometry will tend to keep the search in a low-energy region of the potential surface.
Variations in the parameters can be either random or systematic; in the case of systematic
variations, it is usual to scan the surface first at 'low resolution', then to refine likely looking
regions at high resolution. In the case of random variations, a common problem is that as the
calculation progresses, more and more of the trial structures lead to conformations that have
already been examined.Manymodern software packages have sophisticated algorithms that
can recognize identical conformations, and so reject them from the global search. They also
automatically reject conformations that are too high in energy, compared to
k
B
T
.
Figure 6.4 shows a run using the 'Conformational Search' option of HyperChem. I had
to decide which torsional (dihedral) angles to vary, and I chose just two for this illustrative
calculation: these are called '4-7-8-10' and '5-4-7-8', with the atom numbering shown.
Figure 6.4
Random walk conformation search
The 'Found' table entry shows the number of times that each particular conformation has
been found, and 'Used' shows the number of times it has been used as a starting structure.
Energies are recorded as kcal mol
−
1
.
6.3 Amino Acids
Whilst on the subject of amino acids, Hyperchem has a database of the amino acid residues
that can be quickly joined together to construct a chain. The p
K
of most amino acids is
such that the molecules exist in zwitterion form in aqueous solution, and there is a 'Make
Zwitterion' option. It can be argued that one should include any 'formal' atom charges such
as the zwitterion charges explicitly, and in the case of phenylanine I would modify the
formal charge on each oxygen atom to be
−
1
/
2
electron and add a charge of
+
1 electron on
the nitrogen.
