Role Of Hydrogen Bonds In Protein Folding

Role Of Hydrogen Bonds In Protein Folding

Image credit Duke University

By changing individual atoms in key places in proteins, Duke University chemists have found new evidence for the importance of comparatively weak "hydrogen bonds" in enabling stringlike proteins to fold into the maximally stable shape they need to assume their roles as biological workhorses. Such protein folding immediately after proteins are synthesized is central to their function in the cell.

Eventhough they are much weaker than the preeminent "covalent" chemical bonds that bind atoms in biological molecules, hydrogen bonds are known to occur at key points along the central "backbone" structures of all folded proteins. The hydrogen bonds are created by attractions between adjacent hydrogen and oxygen atoms that are sandwiched into the molecular framework.

How big a role hydrogen bonds actually play in protein folding has been a controversial scientific question, as per Duke associate chemistry professor Michael Fitzgerald. "There's been an ongoing debate about the exact role of those hydrogen bonds," he said in an interview. "Are they really super-important, or are they really negligible?".

Fitzgerald, his graduate student Min Wang and his former graduate student Thomas Wales helped address that question in an effort that took years of work.

One by one, they slightly "mutated" the normal arrangement of atoms in proteins to effectively delete hydrogen bonds at five analogous positions along the structural "backbones" of two different protein molecules that fold in the same pattern. Then they analyzed how each deletion affected the stability of the protein. "Stability" means how low energy, or "relaxed," the protein was.........