Biomedical Engineering Reference
In-Depth Information
a
b
c
d
FIGURE 1.8
(See color insert.)
Possible mechanisms of cross reactivity. Several different
mechanisms were shown to result in receptor promiscuity. (a) Different ligands may form
different elementary bonds in a same binding site [110]. (b) A molecule may display several
unrelated binding sites on its surface. (c) A binding site may be flexible and may accommodate
different ligands [95]. (d) Two unrelated molecules may display some local similarity [103].
In conclusion,
while specificity is a hallmark of biomolecule interactions, promis-
cuity is also a common finding, as testified by the multiplicity of interactions found
in databases.
In addition, the data presented in this brief review illustrate the diversity of situ-
ations and the complexity of the binding mechanisms that involve multiple confor-
mational changes and may depend on structural details of molecular surfaces at the
nanometer scale. Therefore, there is clearly a need for a more accurate description
of protein behavior to interpret more and more refined experimental data. A tentative
way of approaching this goal consists of using computer simulation to try and corre-
late subtile behavioral patterns to structural details. This point will be considered in
the following section.
1.5.3 I
NFORMATION
Y
IELDED BY
C
OMPUTER
S
IMULATION
A conclusion of the results described in previous sections is that (1) experimental
dissection of bond formation and dissociation at the single molecule level brought
an accurate description of many models of biomolecule recognition as highly
multiphasic processes with complex force dependence, (2) experimental study of
isolated protein molecules or molecular complexes with techniques such as X-ray
crystallography or NMR yielded a wealth of structural data with nearly
A
accu-
racy, (3) currently available knowledge of intermolecular forces yielded a relatively
intuitive understanding of the relationship between protein structure and binding
behavior. However, this remains too approximative to allow accurate prediction of
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