In the realm of energy and materials science, a team of researchers from the University of Southern California, led by Professor Dong H. Zhang, has made a significant stride in understanding the role of nuclear quantum effects (NQEs) on the stability of peptides. Their work, published in the journal Nature Communications, sheds light on the microscopic mechanisms underlying the stabilization of peptides, which could have implications for various industries, including energy and biotechnology.
Peptides, the building blocks of proteins, play a crucial role in numerous biological processes. Understanding their stability and folding mechanisms is essential for designing and engineering biomolecules for specific applications. The researchers investigated the impact of NQEs, which arise due to the light mass of hydrogen, on the structure and stability of peptides. They employed advanced computational techniques, including ab initio-level path-integral molecular dynamics simulations and machine-learning interatomic potentials, to explore the role of NQEs in peptide folding.
The study revealed that NQEs systematically destabilize compact three-dimensional structures of peptides, regardless of their secondary structure type or side-chain interactions. Contrary to the conventional belief that hydrogen bonds are central to this phenomenon, the researchers found that the dominant destabilization stems from the quantum vibrations of carbon-hydrogen (C-H) bonds. This finding challenges the existing understanding of isotope effects in biological systems and highlights the importance of considering NQEs in the design and engineering of biomolecules.
Furthermore, the researchers provided microscopic insights into the stabilization of folded peptides upon substitution of hydrogen (H) with deuterium (D) in water (H$_2$O to D$_2$O). They demonstrated that the H/D isotope substitution of active peptide hydrogens, previously considered unimportant, can produce free-energy changes within the range of experimentally observed shifts. This indicates that seemingly small H$\to$D substitutions within peptides can be as important as, or even outweigh, solvent contributions.
The practical applications of this research for the energy sector are manifold. For instance, understanding the stability and folding mechanisms of peptides can aid in the design of more efficient and stable biomolecules for applications such as biofuels, biocatalysis, and biorefinery processes. Additionally, the insights gained from this study can contribute to the development of more accurate computational models for predicting the behavior of biomolecules under various conditions, which is crucial for optimizing energy-related biotechnological processes.
In conclusion, the work of Zhang and his colleagues provides a new interpretation of isotope effects in biological systems and underscores the significance of NQEs in peptide stability. By challenging the conventional wisdom and offering novel insights, this research paves the way for advancements in the design and engineering of biomolecules for a wide range of applications, including those in the energy sector. The study was published in Nature Communications, a prestigious, peer-reviewed journal.
This article is based on research available at arXiv.