Page 33 - Visions of the Future Chemistry and Life Science

22 M. J. SUTCLIFFE AND N. S. SCRUTTON

random mutagenesis – producing modest success, but dependent on being
able to ‘pull out’ an improved enzyme by ‘fishing’ in a very large collection
of randomly modified enzymes. However, development of a suitable test
(i.e. producing the correct ‘bait’) to identify an improved enzyme is intrin-
sically very difficult. Therefore the rational approach, although generally
unsuccessful, cannot be ignored.
Enzymes are large biological molecules – usually proteins – that speed
up chemical reactions. Molecules that speed up chemical reactions, but are
unchanged afterwards, are known as catalysts. The substances that
enzymes act on are known as substrates. Enzymes exhibit remarkable
specificity for their substrate molecules, and can approach ‘catalytic per-
fection’. A popular approach to modelling catalysis has been to visualise an
energy barrier that must be surmounted to proceed from reactants to prod-
ucts (Figure 2.1). The greater the height of this energy barrier, the slower
the rate of reaction. Enzymes (like other catalysts) reduce the energy
required to pass over this barrier, thereby increasing reaction rate. The
structure of the reactant at the top of the barrier is energetically unstable,
and is known as the ‘transition state’. The energy required to pass over the
barrier is the so-called ‘activation energy’ – the barrier is surmounted by
thermal excitation of the substrate. This classical over-the-barrier treat-
ment – known as transition state theory – has been used to picture enzyme-
catalysed reactions over the past 50 years. However, recent developments
indicate that this ‘textbook’ illustration is fundamentally flawed (at least
in some circumstances).
The transition state theory considers only the particle-like properties
of matter. However, matter (especially those particles with smaller mass)
can also be considered as having wave-like properties – this is known as
the wave–particle duality of matter. For enzyme-catalysed reactions, an
alternative picture to transition state theory has emerged from considering
the wave–particle duality of matter. All matter exhibits both particle- and
wave-like properties. Large ‘pieces’ of matter, like tennis balls, exhibit pre-
dominantly particle-like properties. Very small ‘pieces’ of matter, like
photons (of which light is composed), whilst showing some particle-like
properties exhibit mainly wave-like properties. One important feature of
the wave-like properties of matter is that it can pass through regions that
would be inaccessible if it were treated as a particle, i.e. the wave-like prop-
erties mean that matter can pass through regions where there is zero prob-
ability of finding it. This can be visualised, for example, by considering the