23.6 Intermolecular Interactions

321

(of the type often referred to as signal transduction) require the sustained presence of

A in the vicinity of B in order to effect a change (e.g., of conformation) in B that will

then trigger some further event (e.g., in C, also bound to B). A very well-characterized

example of this kind of effect is the photolysis of silver halides. ²⁵ Freshly reduced

Ag will relax back to AgSuperscript plus⁺ if it fails to capture another electron within a characteristic

time (this is the origin of the low-intensity reciprocity failure of photographic film).

Similarly, too weak or too brief an exposure of molecule B to molecule A will result

in the failure of A to trigger any change in B, hence in C, and so on. Therefore, upper KK

alone is inadequate to characterize an interaction.

There are many proteins interacting in a fashion intermediate between the two

extremes of transient and permanent (e.g., transcription factors that must gain a

subunit in order to be able to actively bind to a promoter site).

There are evolutionary constraints imposed on change: A mutation enhancing

the efficiency of an enzyme may be unacceptable because of adverse changes to its

quinary structure.

23.6 Intermolecular Interactions

The simplest, and least specific, interaction is hard-body exclusion. Atoms cannot

interpenetrate due to the Born repulsion. The situation is slightly more complicated

for macromolecules of irregular shape (i.e., with protrusions and reëntrant hollows);

they may be modelled as spheres with effective radii, in which case some interpen-

etration may be possible, in effect.

The Lifshitz–van der Waals force is nearly always weakly attractive, but since it

operates fairly indiscriminately, not only between macromolecules but also between

them and small solvent molecules, it is of little importance in conferring specificity

of interaction.

Most macromolecules are ionized at cytoplasmic pH, due to dissociation (from

–COOH) or addition (to –NHSubscript 22) of a proton, but the charge is usually effectively

screened in the cytoplasmic environment, such that the characteristic distance (the

Debye length) of the electrostatic interaction between charged bodies may be reduced

to a fraction of a nanometre. Hence, it is mainly important for short-range steering

prior to docking.

Hydrogen bonds (H-bonds or HB) have already been encountered (Sects. 15.2,

15.3, 15.5, etc.). A chemical group can be either an HB-donor or an HB-acceptor.

Potentiated by water, this interaction can have a considerable range in typical biolog-

ical milieux—out to tens of nanometres. It is the dominant interparticle interaction

in biological systems. ²⁶

25 See, e.g., Ramsden (1984; 1986).

26 Hydrogen bonding is a special example of Lewis acid–base (AB) or electron donor–acceptor (da)

interactions.