Energy landscape distortions and the mechanical unfolding of proteins.
Molecular simulations and an energy landscape analysis are used to examine the stretching of a model protein. A mapping of the energy landscape shows that stretching the protein causes energy minima and energy barriers to flatten out and disappear, and new energy minima to be created. The implications of these landscape distortions depend on the timescale regime under which the protein is stretched. When the timescale for thermally activated processes is longer than the timescale of stretching, the disappearances of energy barriers provide the mechanism for protein unfolding. When the timescale for thermally activated processes is shorter than the timescale of stretching, the landscape distortions influence the stretching process by changing the number and types of energy minima in which the system can exist.
Lacks
Daniel J
DJ
Department of Chemical Engineering, Case Western Reserve University, Cleveland, Ohio, USA. daniel.lacks@case.edu
D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D006358:Hot Temperature; D008958:Models, Molecular; D015233:Models, Statistical; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013696:Temperature; D013997:Time Factors
D011506:Proteins
Nature. 1997 May 15;387(6630):308-12
9153398
Phys Rev Lett. 2001 Nov 26;87(22):225502
11736406
Biophys J. 2000 Jul;79(1):51-65
10866937
Biophys J. 2002 Dec;83(6):3435-45
12496110
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2031-5
10051589
Science. 1997 May 16;276(5315):1109-12
9148804
J Chem Phys. 2004 Mar 22;120(12):5781-8
15267457
Biophys J. 1999 May;76(5):2439-47
10233061
Science. 1984 Sep 7;225(4666):983-9
17783020
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6166-70
10339559
Phys Rev Lett. 2000 May 15;84(20):4629-32
10990757
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1351-6
9990027
J Mol Biol. 1999 May 7;288(3):441-59
10329153
Phys Rev E Stat Nonlin Soft Matter Phys. 2001 Feb;63(2 Pt 1):021905
11308516
Science. 1997 May 16;276(5315):1112-6
9148805
J Mol Biol. 2002 Sep 27;322(4):841-9
12270718
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5921-8
9600893
Biopolymers. 1992 Jun;32(6):695-709
1643270
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12143-8
12218181
Nature. 2001 Mar 8;410(6825):259-67
11258381
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7254-9
10860990
Biophys J. 2000 Feb;78(2):584-9
10653773
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6521-6
10823892
Annu Rev Phys Chem. 1997;48:545-600
9348663
Phys Rev E Stat Nonlin Soft Matter Phys. 2001 Nov;64(5 Pt 1):051508
11735930
Biophys J. 1998 Aug;75(2):662-71
9675168