Biology Reference
In-Depth Information
any amino acid sequence technically feasible, the currently limited
understanding of protein structure and of the relationship between
structure and function has hindered the application of protein engi-
neering to many complex medical problems.
Rational design of proteins is rooted in the knowledge of the
chemical, physical, and biological properties of proteins. In those
cases when sufficient knowledge of these properties was secured, a
significant progress in protein engineering was attained. 45 On the
other hand, recent progress in the assembly, maintenance, and screen-
ing of large libraries of peptides and proteins and in computational
approaches to protein analysis and design caused an explosive devel-
opment of new strategies in engineering of proteins with predeter-
mined immunological properties. Some of these strategies can be
used for the improvement of immunological activity of proteins and
some for the de novo synthesis of proteins with new immunological
properties.
This chapter reviews major strategies for engineering of viral proteins
with predetermined immunological properties. These strategies can be
classified into “structural,” “functional,” and “focused” approaches. The
structural approach is as close to the real rational design of proteins as
the modern state of science allows. However, because detailed knowl-
edge of a protein's quantitative structure-activity relationship (QSAR) is
often unavailable, this approach results more often in devastating frus-
trations than in exalting victories, which was the main reason for the
development of the functional approach. Also known as “directed evo-
lution,” the functional approach requires no prior knowledge of a pro-
tein's QSAR. Rather, it is based on the availability of a representative
library of peptides or proteins and a selection procedure for the peptide
or protein with the desired activity. It is termed a “functional” approach
because proteins are selected based on specific functions without regard
to structure. The third strategy, referred to here as the focused approach,
avoids the limitations of the other two approaches by applying mathe-
matical modeling to gain new QSAR knowledge and use this knowledge
to design proteins with improved immunological properties. The first
two approaches will be reviewed only briefly below. The chapter high-
lights the focused approach.
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