A protein’s function is linked to its structure. So, in order to understand how a certain protein works in a cell, researchers must first determine its structure. To do so, scientists use X-ray diffraction, irradiating protein crystals that consist of many copies of a single protein lined up and stacked together and then measuring the diffraction of the X-ray beams as they bounce off the atoms of those crystals. From this data, structural biologists can recreate the 3-D shape of the protein.
Since the late ’90s, professor Jeffery G. Saven and his colleagues at the School of Arts and Sciences at UPenn has been developing computational techniques to design proteins and to understand how a specific protein sequence translates to a 3-D crystal structure.
“We’d like to understand protein crystallization better,” said Saven. “We have a database of 100,000 protein structures, and we’d like to use that information to infer something about the interactions within crystals or proteins…and begin to move toward designing a wide variety of high-order structures or take advantage of the self-assembly associated with crystallization.”
In a paper published in the Proceedings of National Academy of Sciences (1), Saven and his team used a combination of theoretical methods and computer technology to identify a three-helix coiled-coil protein design that would crystalize from a potential pool of more than 1022 candidates. Previously, researchers have designed crystal structures using smaller and synthetic molecules, resulting in crystals with limited functions.
“We are dealing with systems and molecules that are much larger than what people have worked with before. It’s a combination of development: the method, the algorithms, and the theory, and also certainly, accelerations in computer hardware, memory capacity, and the speed of processors that have facilitated developments in the field,” said Saven.
In the end, the researchers hope their technique to design a protein crystal will provide a means to investigate the properties in proteins that are important for crystallization. Also, because of their properties and highly customizable exterior surfaces, protein crystals also have exciting industrial applications such as nano-scale building materials.
“You can make all sorts of complicated, potentially information-rich surfaces,” said Saven. “And you could imagine making a variety of different types of crystalline structures or arrangements that might be harder to achieve in the synthetic molecules or the DNA-based systems,” said Saven.
- Lanci, C. J., C. M. MacDermaid, S.-g. Kang, R. Acharya, B. North, X. Yang, X. J. Qiu, W. F. DeGrado, and J. G. Saven. 2012. Computational design of a protein crystal. Proceedings of the National Academy of Sciences (April).