PMID: 9501918Mar 21, 1998

A metastable state in folding simulations of a protein model

Nature Structural Biology
A R Dinner, M Karplus


The native state of a protein is generally believed to be the global free energy minimum. However, there is increasing evidence that kinetically selected states play a role in the biological function of some proteins. In a recent folding study of a 125-residue heteropolymer model, one of 200 sequences was found to fold repeatedly to a particular local minimum that did not interconvert to the global minimum. The kinetic preference for this 'metastable' state is shown to derive from an entropic barrier associated with inserting a tail segment into the protein interior of the serpin-like global minimum structure. The relation of the present results to the role of metastable states in functioning and pathogenic proteins is discussed.


Mar 19, 1992·Nature·D BakerD A Agard
Jun 1, 1992·Biopolymers·J D Honeycutt, D Thirumalai
Jan 16, 1992·Nature·J MottonenE J Goldsmith
Oct 10, 1991·Nature·R W CarrellP E Stein
Jul 20, 1973·Science·C B Anfinsen
Sep 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·H TaniuchiA Sodja
Aug 1, 1995·Proteins·S Govindarajan, R A Goldstein
Sep 29, 1995·Journal of Molecular Biology·V I AbkevichE Shakhnovich
Apr 1, 1995·Protein Science : a Publication of the Protein Society·K A DillH S Chan
Jul 1, 1995·Nature Structural Biology·C M Dobson
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K A DillH S Chan
May 19, 1994·Nature·A SaliM Karplus
Feb 1, 1995·Nature Structural Biology·Q X HuaM A Weiss
Feb 1, 1995·Current Opinion in Structural Biology·M Karplus, A Sali
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M PanF E Cohen
Apr 22, 1994·Science·F E CohenS B Prusiner
Jun 21, 1994·Biochemistry·D Baker, D A Agard
May 16, 1994·FEBS Letters·A J SchulzeR A Engh
Jan 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J KingA Mitraki
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·A R DinnerM Karplus
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·S Zhang, A Rich
Jan 1, 1996·Folding & Design·R L Baldwin
Jan 1, 1996·Folding & Design·Z K Feng, M J Sippl
Jan 1, 1959·Advances in Protein Chemistry·W KAUZMANN
Feb 1, 1958·Proceedings of the National Academy of Sciences of the United States of America·F M Richards


Mar 21, 2003·Biophysical Chemistry·T Lazaridis, M Karplus
Jun 29, 2000·Trends in Biochemical Sciences·A R DinnerM Karplus
Nov 24, 2011·Nature Chemistry·D Thirumalai, G Reddy
Mar 29, 2001·Protein Science : a Publication of the Protein Society·P M HarrisonF E Cohen
Jun 17, 1999·Journal of Molecular Biology·L A Morozova-RocheC M Dobson
Sep 24, 2014·Journal of Theoretical Biology·Yasser B Ruiz-BlancoClivia M Sotomayor-Torres
May 1, 1999·Proteins·T Lazaridis, M Karplus
Sep 24, 1999·Journal of Molecular Biology·A R Dinner, M Karplus
Jan 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·V V Hemanth Giri Rao, Shachi Gosavi
Sep 24, 2002·The Journal of Biological Chemistry·Hana ImMyeong-Hee Yu
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus

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