Folding funnels: the key to robust protein structure prediction

Journal of Computational Chemistry
Corey HardinPeter G Wolynes

Abstract

Natural proteins fold because their free energy landscapes are funneled to their native states. The degree to which a model energy function for protein structure prediction can avoid the multiple minima problem and reliably yield at least low-resolution predictions is also dependent on the topography of the energy landscape. We show that the degree of funneling can be quantitatively expressed in terms of a few averaged properties of the landscape. This allows us to optimize simplified energy functions for protein structure prediction even in the absence of homology information. Here we outline the optimization procedure in the context of associative memory energy functions originally introduced for tertiary structure recognition and demonstrate that even partially funneled landscapes lead to qualitatively correct, low-resolution predictions.

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Citations

Apr 23, 2004·Current Opinion in Structural Biology·José Nelson Onuchic, Peter G Wolynes
Apr 18, 2002·Current Opinion in Structural Biology·Corey HardinZaida Luthey-Schulten
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Joseph A HeglerPeter G Wolynes
Sep 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jin WangVitor B P Leite
Mar 3, 2011·The Journal of Chemical Physics·Olivier Collet
Dec 15, 2006·The Journal of Chemical Physics·Joachim LätzerPeter G Wolynes
Feb 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Garegin A PapoianPeter G Wolynes
Jan 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Corey HardinPeter G Wolynes
May 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·S OłdziejH A Scheraga
Jan 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Adam LiwoHarold A Scheraga
Feb 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey Skolnick
Oct 28, 2008·Journal of Molecular Biology·Gia G MaisuradzeHarold A Scheraga
Feb 14, 2006·Journal of Molecular Biology·Shachi GosaviJosé N Onuchic
Oct 14, 2014·Israel Journal of Chemistry·N P SchaferP G Wolynes
Jan 25, 2005·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Peter G Wolynes
Jun 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tae Wu KimHyotcherl Ihee
Mar 7, 2019·Nature Communications·Richard KosinskiBarbara Saccà
Jan 22, 2014·Physical Chemistry Chemical Physics : PCCP·Chung-Jung Tsai, Ruth Nussinov
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May 1, 2006·Journal of Chemical Theory and Computation·Michael C PrentissPeter G Wolynes
Mar 16, 2004·Science·Julio M Fernandez, Hongbin Li

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