Biology Reference
In-Depth Information
However, most discussions of the systemic approach remain on a metalevel,
and are, for a practising biologist such as myself, ultimately unsatisfactory.
I would rather prefer to give an example, first to explain what I think it means
to be a systems biologist, and second to demonstrate how taking context into
account by using the macroscope has helped me understand deeply and in a
radically new way some functional properties of the cell that were considered to
have been explained long ago. What I also intend showing is that it is not always
necessary to take the whole system into account to understand something; doing
systems biology does not necessarily entail doing 'system-wide' biology (and
vice versa).
Consider a metabolic enzyme, the systems biologist's favourite molecule (the
enzyme marked 1 in Fig. 1a). Consider further a particular kinetic property of this
enzyme, say K
p
, the Michaelis constant for the product of the enzyme-catalysed
reaction, which is an indication of the strength with which the product binds to
the active site of the enzyme (the smaller its value, the stronger the binding).
This enzyme parameter has a specific value that can be measured experimen-
tally. How can we explain why it has one particular value and not another?
There are a number of answers to this question. First, a classical 'enzymological'
answer would explain the value as a function of experimentally determined rate
constants for the elementary steps in the enzyme mechanism. A second, more
modern, 'structural' answer would be based on the three-dimensional conforma-
tion of the active site and the complementary structure of the product molecule,
which could serve as a point of departure for
ab initio
calculations of the value of
the rate constants for binding and dissociation. This type of computational enzy-
mology is fast becoming a reality; it uses the physical and chemical principles of
statistical mechanics and quantum mechanics, and they are implemented in com-
putational form using techniques from computational chemistry (Cunningham
& Bash, 1997). These two approaches are both reductionistic in that they reduce
a property to more elementary properties, here either kinetic or structural; in
essence they use the microscope, zooming into the system which here is the
K
p
(a)
S
P
1
(b)
S
P
1
2
(c)
S
P
M
1
2
3
Figure 1
The functional context of an enzyme that converts a substrate S to a product P.
