%0 Journal Article %1 rose.backbone.sim.2006 %A Rose, George D. %A Fleming, Patrick J. %A Banavar, Jayanth R. %A Maritan, Amos %D 2006 %J Proc Natl Acad Sci U S A %K protein %P 16623–1663 %T A backbone-based theory of protein folding %V 103 %X Under physiological conditions, a protein undergoes a spontaneous disorder º order transition called “folding.” The protein polymer is highly flexible when unfolded but adopts its unique native, three-dimensional structure when folded. Current experimental knowledge comes primarily from thermodynamic measurements in solution or the structures of individual molecules, elucidated by either x-ray crystallography or NMR spectroscopy. From the former, we know the enthalpy, entropy, and free energy differences between the folded and unfolded forms of hundreds of proteins under a variety of solvent
cosolvent conditions. From the latter, we know the structures of
35,000 proteins, which are built on scaffolds of hydrogen-bonded structural elements,
-helix and -sheet. Anfinsen showed that the amino acid sequence alone is sufficient to determine a protein’s structure, but the molecular mechanism responsible for self-assembly remains an open question, probably the most fundamental open question in biochemistry. This perspective is a hybrid: partly review, partly proposal. First, we summarize key ideas regarding protein folding developed over the past half-century and culminating in the current mindset. In this view, the energetics of side-chain interactions dominate the folding process, driving the chain to self-organize under folding conditions. Next, having taken stock, we propose an alternative model that inverts the prevailing side-chain
backbone paradigm. Here, the energetics of backbone hydrogen bonds dominate the folding process, with preorganization in the unfolded state. Then, under folding conditions, the resultant fold is selected from a limited repertoire of structural possibilities, each corresponding to a distinct hydrogen-bonded arrangement of alpha
-helices and
or strands of beta-sheet.

@article{rose.backbone.sim.2006, abstract = {Under physiological conditions, a protein undergoes a spontaneous disorder º order transition called “folding.” The protein polymer is highly flexible when unfolded but adopts its unique native, three-dimensional structure when folded. Current experimental knowledge comes primarily from thermodynamic measurements in solution or the structures of individual molecules, elucidated by either x-ray crystallography or NMR spectroscopy. From the former, we know the enthalpy, entropy, and free energy differences between the folded and unfolded forms of hundreds of proteins under a variety of solvent
cosolvent conditions. From the latter, we know the structures of
35,000 proteins, which are built on scaffolds of hydrogen-bonded structural elements,
-helix and -sheet. Anfinsen showed that the amino acid sequence alone is sufficient to determine a protein’s structure, but the molecular mechanism responsible for self-assembly remains an open question, probably the most fundamental open question in biochemistry. This perspective is a hybrid: partly review, partly proposal. First, we summarize key ideas regarding protein folding developed over the past half-century and culminating in the current mindset. In this view, the energetics of side-chain interactions dominate the folding process, driving the chain to self-organize under folding conditions. Next, having taken stock, we propose an alternative model that inverts the prevailing side-chain
backbone paradigm. Here, the energetics of backbone hydrogen bonds dominate the folding process, with preorganization in the unfolded state. Then, under folding conditions, the resultant fold is selected from a limited repertoire of structural possibilities, each corresponding to a distinct hydrogen-bonded arrangement of alpha
-helices and
or strands of beta-sheet.}, added-at = {2009-03-09T20:10:32.000+0100}, author = {Rose, George D. and Fleming, Patrick J. and Banavar, Jayanth R. and Maritan, Amos}, biburl = {https://www.bibsonomy.org/bibtex/2598c30716214b5c2f92fc75219bcfc4c/huiyangsfsu}, description = {folding.bib}, interhash = {c985242fcd601879084bd9d947bb1d9b}, intrahash = {598c30716214b5c2f92fc75219bcfc4c}, issue = {45}, journal = {Proc Natl Acad Sci U S A}, keywords = {protein}, month = { November}, pages = {16623–1663}, timestamp = {2010-11-12T05:01:51.000+0100}, title = {A backbone-based theory of protein folding}, volume = 103, year = { 2006} }