ASU student first author on dynamic water-protein interactions research article

In the world of large, macroscopic objects, it is often easy to understand what and why something is happening. For example, water flows downhill due to the presence of gravity and the decrease in potential energy. On the molecular level, however, additional factors, such as entropy, must be considered to understand the outcome of events. This is especially the case for biomolecular processes that involve many moving parts, whose interactions with each other determine the overall change in potential energy and entropy.

In biological systems, proteins interact with water located within or between cells. To better understand these interactions, ASU online School of Molecular Sciences alumna Tawny Fajardo and School of Molecular Sciences Assistant Professor Matthias Heyden, through computer simulations of a small peptide, studied the underlying components of the potential energy and entropy that determine the peptide’s structural and dynamical properties.

Their results are published in "Dissecting the Conformational Free Energy of a Small Peptide in Solution" in The Journal of Physical Chemistry B.

Fajardo, first author of this paper, at the time of the study was an online undergraduate student in the online School of Molecular Sciences biochemistry program. The computer simulations were carried out remotely utilizing ASU’s Research Computing infrastructure. 

Using all-atom simulations of a small peptide (essentially a mini-protein) in water, they analyzed changes of the peptide’s conformation and corresponding changes in potential energy and entropy. Combining multiple techniques, these changes were further broken down into distinct contributions. Interactions between the peptide and surrounding water were found to strongly influence which peptide conformations are likely to be observed and how frequent transitions between distinct conformations can be expected. Despite the simplicity of the studied system, their results reveal the critical role of water as the universal solvent of biomolecular processes.

“Our study provides an example for the decomposition of thermodynamic driving forces in a biomolecular system,” Heyden said. “Applied to more complex systems, our approach may improve our future understanding of complex biochemical processes and enhance our ability to design artificial enzymes or drugs with high affinity and specificity for their targets.”

Tijana Rajh, director of the School of Molecular Sciences, said, “This study is a testimony to the quality of our online program. The role of water in structural conformations of proteins and protein functioning is one of the long-standing problems in various fields ranging from natural photosynthesis to cancer studies. It is noteworthy that our online program has given the necessary tools to an undergraduate student to tackle such a complex and important problem.”

Future research will build on the insights and methods developed for this project to understand the driving forces of biochemical processes involving biomolecular machines and enzymes, which are key to biological life.