Chemistry Reference
In-Depth Information
quality of the loops generated (
ab initio
fold prediction). In order to select the best
loop conformation, molecular dynamics, for example, can be used to minimize the
energy function. A guide to model loop regions in the knowledge-based approach
would be, for example, a segment of equivalent length in a homologous protein.
The conformation should be the same for loops that possess the same length and
amino acid character allowing direct transfer of coordinates to the model
structure. Loop search protocols can also be used. Loops can be retrieved as well
from peptide segments in other proteins.
Regarding the fifth stage,
i.e.
side chain modeling, we note the following.
Backbone conformation and features of the local environment can influence
considerable the side chain orientation. Consequently, the accuracy of the
backbone coordinates also influences significantly the accuracy of the side chain
localization. In addition, side chains (with various degrees of freedom) can adopt
various energetically allowed conformations. At high levels of sequence identity,
it is sometimes simpler to just copy entirely conserved residues from the template
to the model. A knowledge-based approach (rotamer libraries) can also be used to
place the side chains. Rotamers can be tried and scored successfully. The key lies
in the fact that certain backbone conformations strongly favors certain rotamers.
Regarding the sixth step for model optimization we indicate the following.
Minimization of the model is important to relax geometric chain/close contacts
and regularize angle geometry/local bonds. Minor inconsistencies and steric
clashes should be removed. Energy minimization and molecular dynamics is
typically used for optimization.
The last stage is the model validation. It is important to assess quality/reliability of
the homology model built. The errors in the final model depend on the number of
errors in the template structure. The model's errors also depend on the percentage
of sequence identity. The stereochemistry quality also depends on the accuracy of
the template structure. Bond torsions, planarity of peptides, bond lengths, torsions
and angles can be determined and compared.
The close packing of segments of secondary structures influences the high packing
densities of proteins. Interior packing can strongly influence the stability.
