Biology Reference
In-Depth Information
technique (PROSA, “protein sequence analysis”) used a simple statis-
tical procedure based on the frequencies of residue classes in a set of
aligned amino acid sequences. It generated consensus sequences with
a physicochemical property pattern thought to constitute an underly-
ing functional or structural feature in common. The second design
technique (SME, “simulated molecular evolution”) used ANNs and
an evolutionary algorithm for peptide development. The neural net-
works were used to extract essential cleavage site features from a set
of known cleavage and non-cleavage site examples. After successful
feature extraction these systems provided a mathematical model of SP
I target sites that was used as a heuristic fitness function for a system-
atic evolutionary search in sequence space.
Artificial Peptide and Protein Design
An interesting idea that emerges from these strategies for
de novo
pep-
tide/protein design is the possibility of designing truly artificial can-
didates. Since knowledge of QSAR can be extracted from the neural
network, it is possible to include non-natural (artificial) residues in the
design strategy. This can lead to peptide/protein-like structures that
are suitable as leads for immunotherapeutic and diagnostic develop-
ment. Certainly, if successful, protein engineering will break loose
from the natural architectural framework constrained to a 20 amino
acid domain. In fact,
de novo
design of peptides/proteins with desired
functions should be approached in the same way that modern engi-
neering has modified and changed our environment.
The first step in designing a building is to experiment with many
different ideas for the basic form, volume, and the structure of the
building to meet its pre-specified function. Added to this architectural
designing process is the design of raw materials to specification. Raw
materials like iron and aluminum, or building blocks like cinder blocks
and bricks are physically and chemically modified to specific strengths
and molded to predetermined shapes. All of these factors are needed
to achieve the final structure and function for which a building has been
designed. Similarly, amino acids, the raw material and building blocks
