Photo credit: www.sciencedaily.com
Advancements in Polypeptide Design for Biotechnology and Materials Science
A collaborative research effort involving Rensselaer Polytechnic Institute and the University of Washington has unveiled a methodical high-throughput design protocol aimed at the virtual screening and creation of novel polypeptide-based molecules. These molecules are characterized by their ability to form regular secondary structures, which are critical in various domains such as biology and materials science. The project is notably led by Dr. Gaetano Montelione, a prominent figure in chemistry and chemical biology at RPI, alongside Dr. David Baker of the University of Washington, who recently garnered recognition as a co-recipient of the 2024 Nobel Prize in Chemistry for his pioneering work in de novo protein design.
Regular secondary structures like alpha helices and beta sheets serve as the essential framework within protein architecture. Understanding these structures plays a crucial role in decoding protein folding and function, facilitating drug target identification, and exploring the molecular mechanisms that contribute to various diseases. The research team delved into over 200,000 combinations of 130 non-biological amino acids, each selected for their unique chemical properties, thus expanding the landscape of potential polypeptide secondary structures. This innovative methodology, crafted by Dr. Adam Moyer, led to the identification of hundreds of unique low-energy repeating structures.
“We characterized 10 newly identified dipeptide repeating structures using circular dichroism spectroscopy and comparison with their calculated spectra,” noted Montelione. The computed spectra aid researchers in predicting light absorption or emission at certain wavelengths, providing insights into the molecular geometries of the polymers. The 10 dipeptide repeat polymers showcased ordered structures consistent with expectations. Further investigations utilizing NMR and X-ray crystallography on two of the polymers reinforced their coherence with computational models, corroborating the robustness of the design strategy. The computational framework established is adaptable for a diverse array of polymers, which could lead to extensive applications in materials design.
“The Institute for Protein Design is at the forefront of utilizing artificial intelligence and computational techniques to engineer novel proteins and polypeptides for a multitude of biotechnology and materials science purposes,” commented Montelione. “Our partnership amplifies the influence of these synthetic proteins, while simultaneously integrating advanced technologies at RPI that bolster our initiatives aimed at innovating biomolecules capable of modulating protein-protein interactions relevant to cancer biology and viral infection mechanisms.”
Dr. Curt Breneman, dean of RPI’s School of Science, remarked, “This study lays the groundwork for designing new materials tailored with specific characteristics. It also enhances our understanding of how to model both the structure and stability of polymers.”
The research was spearheaded by Adam Moyer, a recent graduate from Baker’s lab, alongside Theresa Ramelot, a senior research scientist in Montelione’s lab. Other contributors included Roberto Tejero from RPI, as well as University of Washington’s Alex Kang, Asim K. Bera, and Patrick J. Salveson; Mariano Curti and Elisabet Romero from the Barcelona Institute of Science and Technology; Margaret A. Eastman from Oklahoma State University; and Carles Curutchet from Universitat de Barcelona. Montelione, Ramelot, and Tejero are members of RPI’s Center for Biotechnology and Interdisciplinary Studies.
Source
www.sciencedaily.com