Study Determines That How Proteins Move May Influe
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Proteins come in various shapes, making it hard to determine how they move and, in turn, how they function. A study conducted by researchers at the Karolinska Institute has discovered a new target for brain tumors through the use of computer simulations.
Laura Orellana, a biophysicist at the institution’s Department of Oncology-Pathology, led the study, which looked into how proteins moved. The study used data from the Protein Data Bank, which comprises decades of information on the 3D structures of different kinds of biological molecules, including proteins. This data is based on experimental techniques such as nuclear magnetic resonance (NMR) or X-ray crystallography.
Orellana stated that the database contained roughly 60,000 known structures of human proteins; these images, however, still didn’t demonstrate how proteins moved. This, the researcher argued, was an issue since a protein’s function lays in its movement.
In an effort to determine how proteins moved, Orellana used computer simulations based on images of different proteins that had been animated using the relevant laws of physics.
For the study, the researchers focused on how the epidermal growth factor receptor gene (EGFR) moved in glioblastoma, an aggressive type of cancer that occurs in the spinal cord and/or brain. To begin, Orellana simulated the oncogene EGFR (HER1). EGFR is a trans-membrane protein that is involved in the cell signaling pathways that control survival and cell division. In some cases, mutations in the EGFR cause HER1 proteins to be produced in higher amounts than normal. This then causes cancer cells to divide at a faster rate.
In lung cancer, the mutated parts of the HER1 protein are found inside the cell. However, in glioblastoma, these parts are found outside. The study demonstrated that in glioblastoma, mutations caused the extracellular part of the HER1 protein to move. This activated the intracellular part in a way that drove the development of tumors, noting that this had not been observed in lung cancer.
Orellana hypothesized that this movement affected the effectiveness of cancer treatments.
In the report, the biophysicist highlighted that the computer simulations also uncovered a surface where antibodies could attach. This is after the group’s experiments confirmed that certain antibodies could bind to this specific surface and drastically hinder glioblastoma growth.
Orellana emphasized the importance of understanding how proteins worked and moved at the atomic level, noting that since drugs bound to special pockets in proteins, movement could influence how drugs bound to biological molecules.
These discoveries could potentially be of great interest to companies such as CNS Pharmaceuticals Inc. (NASDAQ: CNSP) that specialize in developing treatments for cancers that affect the brain as well as the central nervous system.
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