Biology Reference
In-Depth Information
152
BACKBONE STRUCTURE PREDICTION
Therefore, further reduction of choices for each amino acid residue
seems to be essential for this matching process to be useful in predicting
three-dimensional structures of proteins. Essentially only one choice for
each residue will be needed. One way of achieving this goal is to consider
all other proteins homologous to the one under study. For example,
presumably cytochromes c from various species should fold into similar or
nearly identical three-dimensional structures. However, locally, their amino
acid sequences may be different. For a certain position, the choices
can be different for each of these sequences. The required choice for the
collection of all these sequences must be common to all of them. As a
result, some of the positions of cytochromes c may have only one choice for
their
angles. Other positions can still have several choices.
Short Peptide Hormones
Another possible application of this matching process is to short peptides
such as the nine amino acid neurohypophyseal hormones (Honig
et al
.,
1973). Even in the case of several choices for each amino acid
residue, the total number of combination of choices is relatively small since
there are only a few residues. These peptide hormones do not form crystals
easily. Thus their three-dimensional structures cannot be analyzed by X-ray
diffraction studies. On the other hand, nuclear magnetic resonance (NMR)
can be a powerful physical tool to determine their structures. Thus, results
based on theoretical predictive methods can be compared with experimental
NMR findings, although the solvent in the NMR study may not be water.
Homologous sequences are also used to reduce the number of choices.
They are listed in Table 6-3. The presence of a disulfide bond between Cys
1 and Cys 6 can provide additional restrictions of the angles.
However, the N-terminal and C-terminal residues, i.e. Cys 1 and Gly 9, can
have some flexibility. Energy minimization with various potential functions
between non-bounded atoms as discussed in the previous Chapter can be
used to refine the angles. In the process, the Cys 1 and Cys 6 disulfide
bond is established and steric hindrance avoided.
