STAT+: Undruggable \u2018disordered\u2019 proteins become druggable with new AI techniques from David Baker
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For decades, structural biologists shoved what looked like shoddy data in the back of their closets, embarrassed. While attempting to gather the structures of proteins, they would sometimes find that all or at least a portion of the protein would just not show up correctly in the data.\u00a0<\/p>\n
Joel Sussman, a former head of the Protein Data Bank, remembers when he found his first intrinsically disordered protein, though it wasn\u2019t called that at the time. He showed it to a collaborator. \u201c\u2018Oh, Joel, you\u2019re not a very good biochemist. Obviously, it has a structure and you\u2019re confused,\u2019\u201d he recalled her saying.<\/p>\n
Most proteins fold into shapes with distinct elements: the ordered spiral of an alpha-helix, like a piece of cavatappi pasta; or beta sheets, like a slice of a lasagna \u2014 squiggly lines of pasta amino acids held parallel to each other with cheesy and saucy hydrogen bonds. A central tenet of structural biology is that a protein\u2019s structure dictates its function. But around the same time<\/a> that the world was preparing for Y2K, structural biologists finally began admitting that \u2014 just as Sussman and other scientists had seen \u2014 not all proteins have a permanent shape. A surprisingly large amount of important proteins (in fact, over half of all proteins in eukaryotes<\/a>, it\u2019s estimated) have strands of wiggly \u201cspaghetti\u201d in them.\u00a0<\/p>\n Continue to STAT+ to read the full story\u2026<\/a><\/p>\n<\/div>\n