At last, computers are beginning to unravel the origins of enzyme catalysis.

Mathematical models are now shedding so much light on the way enzymes accelerate biological reactions that they are helping researchers to integrate two fundamental but contradictory hypotheses concerning the mechanisms involved, says Vicent Moliner, a theoretical chemist at the Universitat Jaume I of Castelló in Spain.

Under the transition state theory, an enzyme rearranges itself to bond with the unstable 'transition state' that a substrate becomes during its transformation into something else. In so doing, the enzyme provides a much more stable transition state that helps to accelerate the reaction. Under the Michaelis complex theory, however, it is the substrate rather than the enzyme that rearranges itself to stabilise the transition state, and so speed the reaction along.

In this tutorial review, Moliner shows how both theories can explain the action of an enzyme.

'Basically we now have the technology [computer simulations] to find out how enzymes really work', comments Arieh Warshel, professor of chemistry at the University of Southern California in Los Angeles, 'and the difficulty is mainly in teaching people that they must define their hypotheses before one can see if these hypotheses are correct.'

Katharine Sanderson