Chemical reactions in the cell are catalyzed by enzymes, which are protein molecules that speed up reactions. Each protein catalyzes a specific reaction. In a chemical reaction, two molecules collide and exchange atoms; the enzyme is the third party, the “midwife to the reaction.”
But the molecules have to collide in a certain way for the reaction to occur. The enzyme binds to the molecules and lines them up, forcing them to collide in the “right” way, so the probability that the molecules will exchange atoms is much higher.
“Instead of just watching what the molecules do, we can mechanically prod them,” said Zocchi, the senior author of the research.
To do that, Zocchi, Tseng and Wang, attached a controllable molecular spring made of DNA to the enzyme. The spring is about 10,000 times smaller than the diameter of a human hair. They can mechanically turn the enzyme on and off and control how fast the chemical reaction occurs. In their newest research, they attached the molecular spring at three different locations on the enzyme and were able to mechanically influence different specific steps of the reaction.
“We have stressed the enzyme in different ways,” Zocchi said. “We can measure the effect on the chemical reaction of stressing the molecule this way or that way. Stressing the molecule in different locations produces different responses. If you attach the molecular spring in one place, nothing much happens to the chemical reaction, but you attach it to a different place and you affect one step in the chemical reaction. Then you attach it to a third place and affect another step in this chemical reaction.”
The scientists studied the rate of the chemical reactions and reported in detail what happened to the steps of the reactions as they applied mechanical stress to the enzyme at different places.
“Standing on the shoulders of 50 years of structural studies of proteins, we looked beyond the structural description at the dynamics, specifically the question of what forces – and applied where – have what effect on the reaction rates,” Zocchi said.
While Zocchi’s research may have applications for medicine and other fields, he emphasizes the advance in knowledge itself.