Biomedical Engineering Reference
In-Depth Information
The goal of this chapter is to present as palatably as possible a number of bio-
logical processes and recent methodological advances that played an important role
in the development of DFS and may benefit from this growing domain. The first
section includes selected examples of biological situations that are heavily depen-
dent on biomolecular recognition. This will be the basis for defining the questions
we need to ask. The next section is a brief outline of recent progress done in the
study of molecular interactions, particularly at the single bond level, which shaped
the present state of the art. The next section is intended to define and analyze the
parameters required to provide an adequate account of biomolecule interactions, that
is, to include the pieces of information that are needed to predict the behavior of a
given ligand-receptor couple under physiological conditions. The last section gives
a brief description of the application of conventional physical-chemical knowledge
and newer computer simulation methods to the study of links between biomolecule
structure and association properties. Admittedly, the field of biomolecule interac-
tions is too vast to be exhaustively discussed in the limited space available. Also, it
is unavoidable that the topics selected in this chapter should reflect the limitations of
the author's fields of competence and interest. Therefore, I apologize for the omis-
sion of many key references that would certainly have enriched this presentation.
1.2 WHAT IS THE USE OF BIOMOLECULAR INTERACTIONS?
The goal of this section is to describe several important biological processes to illus-
trate the role of biomolecule interactions and the constraints that must be met.
1.2.1 C
ELL
S
TRUCTURE:
S
TATICS AND
D
YNAMICS
Clearly, any living cell or organism would fall into pieces in absence of the molecular
interactions linking their components. It is important to emphasize that both quali-
tative and quantitative properties of these interactions are essential. Thus, it is well
recognized that cell formation requires an autoorganization capacity of biomolecules
that must be able to bind to each other with sufficient
specificity
to avoid durable pres-
ence of potentially harmful molecular interactions [188]. In addition, the rheological
properties of cells are considered to be driven by the properties of the underlying
cytoskeletal elements, which are themselves dependent on the
kinetic
and
mechan-
ical
properties of intermolecular associations [192]. These points are important in
view of the recently recognized importance of cell mechanics in situations of med-
ical interest such as cancer cell metastasis [79] [165] or lethal inflammatory pro-
cesses such as the acute respiratory disease syndrome [135]. Cell shape is consid-
ered to be highly dependent on the dynamic organization of a network of rod-like
structures including actin microfilaments, tubulin microtubules, and intermediate fil-
aments. These are highly plastic structures whose growth or retraction is determined
by a variety of interaction events, and particularly polymerization/depolymerization
as a consequence of tunable
kinetics
of monomer association or dissociation. Other
important events are movements driven by the so-called
motor molecules
such as
myosin or kinesin that are able to generate force-dependent displacements. Much
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