Heavy water key to 'groundbreaking work' on electron transfer in proteins by ASU professor
Arizona State University’s Dmitry Matyushov, professor in the School of Molecular Sciences and the Department of Physics, has spent years studying how electrons make their way through some important protein molecules.
He recently published results from computer simulations that show that the rate of electron hops within proteins is determined not by the rate of electron tunneling but by the rate of the protein changing its configuration to make tunneling possible. This exciting possibility brings protein identity into the picture: Any property that changes a protein's dynamics and flexibility can be used as a tuning knob to adjust the rate of charge transport across biological membranes.
“Matyushov’s groundbreaking work on protein energetics and structural dynamics has opened a new window into the role of protein movement across many timescales in reaction mechanism,” said Professor Tijana Rajh, director of the School of Molecular Sciences, which is part of the College of Liberal Arts and Sciences. The trapping of electrons by protein water allows the unidirectional flow of electrons, called the the diode effect, in energy chains of biology.
All the energy of biology is produced by energy chains made of membrane-bound proteins that use the energy of light in the photosynthesis of bacteria and plants or the energy of food in the cellular mitochondria in animals. How the energy of light or food is converted to the energy of the cell is mostly related to the question of how these specific proteins shuttle electrons across the cellular membrane.
As far back as 1966, scientists DeVault and Chance established the phenomenon of quantum mechanical tunneling in biology. Tunneling is a quantum phenomenon in which a particle is able to access a classically forbidden region. This often manifests as a “hopping” motion in which it appears that a particle has overcome an energy barrier that is greater than its kinetic energy.
“Since 1966, the prevailing dogma in molecular biophysics is that the rate of electron transport in photosynthesis and mitochondrial respiration is determined by tunneling of electrons between cofactors immersed in the protein matrix,” Matyushov explained.
Slowing of the charge transport rate upon water's deuteration was also recently confirmed in single-molecule studies in Professor Stuart Lindsay’s lab. Lindsay is an ASU Regents Professor and director of ASU’s Center for Single Molecule Biophysics. He is also a professor in the School of Molecular Sciences and the Department of Physics.
Lindsay's recent work suggests that protein identity can strongly affect the rate of charge transport through proteins. Tunneling is still important at longer distances, but charge transfer within proteins is mostly determined by their dynamics and flexibility.
Matyushov pondered how to prove that this new understanding was correct. “One has to change the charge transport conditions in such a way that the dynamics of the system is altered without affecting the activation barrier that the system needs to climb to allow electrons to tunnel.”
The problem seemed to have no solution until he realized that replacing normal water with heavy water would allow for such an experimental or computational test.
Hydrogen is the lightest and most abundant element in the universe. Deuterium is an isotope of hydrogen and has a neutron in its nucleus, which hydrogen lacks, making it heavier than hydrogen. When hydrogen atoms in water are replaced with deuterium, heavy water is the result. Heavy water is toxic, but specific reasons for its adverse health effect are not clear. It might well turn out that the reason is in the slowing down of mitochondrial function and energy metabolism, according to Matyushov.
Heavy water, it turns out, forms stronger hydrogen bonds with charged amino acids of the protein without significantly affecting the activation barrier.
Recent computer simulations performed by Setare Sarhangi, a postdoctoral fellow in Matyushov’s lab, compared charge transfers within the protein azurin in both normal and heavy water. As expected, deuteration did not affect the activation barrier, but strongly slowed the protein dynamics down by a factor of 25.
In full agreement with theoretical predictions, the overall rate of charge transfer was greatly reduced.