Darwinian biophysics: Electrostatics and evolution in the kinetics of molecular binding

At the molecular level of biology, the competition for favorable outcomes has been shaped by evolution, just as in more familiar examples from ecological biology. At both levels, this competition is often based on raw speed. There are differences, of course. Most notably, a race between molecules is more often determined by diffusional dynamics than by inertial dynamics. The driving forces on molecules typically comprise electrostatic nudges rather than thundering hooves digging into soil. Electrostatic interactions can be surprisingly effective, however. The rate of degradation of the neurotransmitter acetylcholine by the synaptic enzyme acetylcholinesterase is known to be increased by a factor of up to a few hundred as a result of “electrostatic steering” of the positively charged acetylcholine molecule toward the predominantly negative active-site region of the enzyme (1). This tends to optimize the clearing and resetting of neuromuscular junctions and other cholinergic synapses, which offered a clear competitive advantage to our successful ancestors, relative to more sluggish individuals of their species who faced the same predators. Such selective pressures are also recorded in proteins at the next level of a hierarchy, in some of the venom molecules of snakes such as the green mamba that prey on small mammals in sub-Saharan East Africa. The green mamba toxin fasciculin-2 is a small protein whose positively charged surface is attracted to, and clamps down on, the active-site entrance of acetylcholinesterase, causing muscular activity of the unfortunate rat or other prey to cease. Here, again, the binding involves electrostatically steered diffusion, and the binding speed is increased by a factor of up to a few hundred by the electrostatic attraction between the proteins (1). Many other examples of electrostatically steered, diffusion-controlled processes are now known, including such familiar ones as the polymerization of actin (2, 3). In a recent issue of PNAS, a new article by Qin and Zhou greatly deepens our insight into these important processes, and extends the range of analysis to include reactions in which the rates may be influenced by events following the initial diffusional encounter (4).