Scientists develop program to define stable sequences for collagen synthesis
Rice University researchers have made a major step toward synthesizing custom collagen, having learned how to make collagen, and are now digging into its molecular structure to see how it forms and interacts with biological systems.
Jeffrey Hartgerink, an associate professor of chemistry and of bioengineering, and his former graduate student Jorge Fallas, now a postdoctoral researcher at the University of Washington, wrote a new computer program that predicts the most stable structures of nanometer-sized collagen.
In nature, these small structures link into chains that serve as connective tissue in the body. Hartgerink and Fallas followed up the computer research by making and testing the collagen detailed in their calculations.
In their work, Hartgerink and Fallas analyzed charged interactions between amino acids that attract one strand to another to form the triple helix. "We look at positively charged and negatively charged amino acids and where they need to be aligned to result in stabilization," Hartgerink said.
Their computer program calculates the stability of each possible alignment of a given set of peptide strands to find the best matches of positively and negatively charged amino acids.
It then assigns each set a score, based on the net positive or negative charge of the entire helix.
"If we have a positive charge in a peptide sequence, it will destabilize the triple helix, and we score that as a minus 1," Hartgerink said.
"If we have a negative charge, that also destabilizes the helix and we also score that as a minus 1. But if those charges line up in what we call the axial geometry, it negates the destabilization. This triple helix would have a score of 0, which is good.”
An example of the program is shown in the picture where the colored portion of the molecule shows positively charged lysine and negatively charged aspartate interacting in the required axial geometry that stabilizes the triple helix.
As a result, the study, which was published in the online journal Nature Communications, will be of interest to physicians and scientists who work in reconstructive surgery, cosmetics and tissue engineering, seeking to develop further understanding of collagen structures.
Collagen is a type of protein found extensively throughout the body that supports skin, internal organs, muscles, bone, and cartilage.