Bioorganic Chemistry
7
+
+
+
+
+
+
+ −
+
+
+
+
+ +
+ −
+ −
Case 1:
Chemical and
steric
complementarity
Complexation driven by a combination of steric and chemical complementarity.
Steric
=
size and shape
Chemical:
(1) charge/charge
(2) partial charge/partial charge
d
+
d
(3) nonpolar/nonpolar
Case 2:
Steric
complementarity
but chemical
clash
Case 3:
Chemical
complementarity
but steric clash
Case 4:
Chemical
complementarity
and suboptimal
steric match
LP
L
P
+
Fig. 5
Schematic representation of protein (P) ligand (L) association. Case 1
represents the optimal situation with simultaneous steric and chemical
complementarity.
reflects the overall stability of the sys-
tem, is a combination of two terms,
enthalpy (
1
H
)andentropy(
1
S
) follow-
ing the equation
1
G
=
1
H
T
1
S
.
An overall negative
1
G
bind
is indicative
of a favorable process, so the trend is
that reactions that have a decrease in en-
thalpy and an increase in entropy will tend
to occur spontaneously, although either
term can overcome the other. Enthalpy
refers to the change in attractions and
repulsions that occur during the reac-
tion that are the result of forces (such
as coulombic
forces and
intramolecu-
lar forces such as bond stretching.) The
entropic term refers to the change in
the ‘‘randomness’’ in the system or the
number
of
conFgurations
the
system
can adopt.
±or the most efFcient binding of the
ligand, it should have both steric and chem-
ical complementarity to the target site.
Steric complementarity refers to the shape
of the ligand versus the shape of the bind-
ing site. Chemical complementarity refers
to the appropriate matching of surfaces on
the ligand with the binding site. On av-
erage, surface elements that contact each
other should have opposite charges on the
ligand and the site to allow for effective
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