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Picturing Proteins
Computer models may reveal the protein collagen’s role in disease
By Stu Hudson

Assistant professor collin Stultz is taking a bottom-up approach to understanding diseases such as arthritis, cancer, and heart disease. A researcher in electrical engineering and computer science and health sciences and technology, Stultz has trained his sights on a protein best known as an ingredient in beauty products: collagen.

All three diseases involve enzymes that break down collagen, which provides the scaffolding for our skin, cartilage, bone, and connective tissue. For example, some tumors expel enzymes that destroy surrounding tissue, freeing malignant cells to spread. Right now, little is known about how these enzymes interact with collagen at the molecular level. But Stultz may have found the key to a deeper understanding. He has created a new computer model of collagen that might reveal its Achilles’ heel.

When Stultz began his work almost five years ago, computer simulations showed only how collagen looked in the crystalline state of samples prepared for x-ray diffraction, an imaging method used to determine protein structures. After examining the amino acid chains that make up collagen, Stultz guessed that the winding, kinked protein partially unfolds at higher temperatures or in the presence of other molecules in the body—revealing a part of its anatomy that is vulnerable to enzymes that can degrade it.

To explore this conjecture, he constructed a computer model of the unfolded protein and used it to estimate the readings that the protein would give when subjected to certain spectroscopic techniques. He tested these predictions experimentally and found that the data closely matched his model. Stultz achieved a working model of collagen last fall.

Stultz and his team hope that by further refining the model to reflect collagen’s reactions to specific diseases, they can discover how to maintain the protein’s integrity, thus staving off the progression of arthritis, cancer, and heart disease.