Scientists Use Direct Coupling Analysis to Investigate Complex Molecular Machines

Open, feed, cut. Such is the humdrum life of a motor molecule, the subject of new research at Rice University, that eats and excretes damaged proteins and turns them into harmless peptides for disposal. The why is obvious: Without these trash bins, the Escherichia coli bacteria they serve would die. And thanks to Rice, the how is becoming clearer. Biophysicists at Rice used the miniscule machine – a protease called an FtsH-AAA hexameric peptidase – as a model to test calculations that combine genetic and structural data. Their goal is to solve one of the most compelling mysteries in biology: how proteins perform the regulatory mechanisms in cells upon which life depends. The Rice team of biological physicist Dr. José Onuchic and postdoctoral researchers Drs. Biman Jana and Faruck Morcos published a new paper on the work online on March 7, 2014 in a special issue of the Royal Society of Chemistry journal, Physical Chemistry Chemical Physics. The special issue edited by Rice biophysicist Dr. Peter Wolynes and Dr. Ruth Nussinov, a researcher at the National Cancer Institute and a professor at the Sackler School of Medicine at Tel Aviv University, pulls together current thinking on how an explosion of data combined with ever more powerful computers is bringing about a second revolution in molecular biology. The paper describes the Onuchic group’s first successful attempt to feed data through their computational technique to describe the complex activity of a large molecular machine formed by proteins. Ultimately, understanding these machines will help researchers design drugs to treat diseases like cancer, the focus of Rice’s Center for Theoretical Biological Physics. “Structural techniques like X-ray crystallography and nuclear magnetic resonance have worked quite well to help us understand how smaller proteins function,” Dr.
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