Molecular Simulations Find Stable Structures in Fragments of Protein G.
We perform all-atom computer simulations on nearly one hundred 6-, 8-, 10-, and 12-mer peptide fragments of protein G, and look for stable states. We simulated by replica-exchange molecular dynamics using Amber7 with the parm96 force-field and a GB/SA (generalized-Born/solvent accessible) implicit solvent model. We find that useful diagnostics for identifying stable converged structures are the conformational entropy and free energy of each state. A large gap in the ground-state free-energy, and a low entropy indicate convergence to a single preferred peptide conformation. We find that a non-negligible fraction of such structures have some native-like character. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.
Urbič
Tjaša
T
National Institute of Chemistry Slovenia, Ljubljana, Slovenia.
Urbič
Tomaž
T
Avbelj
Franc
F
Dill
Ken A
KA
J Mol Biol. 2001 Feb 23;306(3):397-402
11178900
Biochemistry. 2000 Mar 21;39(11):2894-901
10715109
Nat Struct Biol. 1995 Nov;2(11):999-1006
7583674
J Chem Phys. 2005 Oct 15;123(15):154105
16252940
Proteins. 2005 Jan 1;58(1):45-52
15521057
Science. 2005 Sep 16;309(5742):1868-71
16166519
PLoS Comput Biol. 2006 Apr;2(4):e27
16617376
Protein Sci. 1997 Jan;6(1):162-74
9007989
Science. 2001 Oct 5;294(5540):93-6
11588250
Proteins. 2001 May 1;43(2):186-202
11276088
Biochemistry. 2003 Jul 8;42(26):7976-85
12834350
Nature. 1996 Apr 25;380(6576):730-4
8614471
Proteins. 1995 Oct;23(2):129-41
8592695
Proteins. 2003;53 Suppl 6:436-56
14579333
Biochemistry. 1993 Jun 29;32(25):6337-47
8518279
J Mol Biol. 1998 Aug 21;281(3):565-77
9698570
Proteins. 2003 Nov 1;53(2):148-61
14517967
Nat Struct Biol. 1998 Jul;5 Suppl:499-503
9665178
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2362-7
15677316
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18914-9
16365306
J Mol Biol. 1963 Jul;7:95-9
13990617
Annu Rev Biochem. 1982;51:459-89
6287919
J Mol Biol. 1992 Aug 5;226(3):795-817
1507227
Trends Biochem Sci. 1999 Jan;24(1):26-33
10087919
Proteins. 1995 Jun;22(2):81-99
7567969
J Mol Biol. 2004 Jul 23;340(5):1131-42
15236972
Proteins. 2005 May 1;59(2):196-204
15726585
J Chem Theory Comput. 2007 Jan;3(1):26-41
26627148
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11987-92
17620603
Protein Sci. 1999 Jun;8(6):1320-31
10386882
Curr Opin Struct Biol. 2005 Jun;15(3):285-9
15939584
J Comput Chem. 2002 Jan 30;23(2):245-66
11924737
Biopolymers. 2000-2001;56(4):275-91
11754341
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1942-6
7680482
Curr Opin Biotechnol. 1996 Aug;7(4):417-21
8768900
Nat Struct Biol. 1994 Sep;1(9):584-90
7634098
Proc Natl Acad Sci U S A. 1989 Jul;86(14):5286-90
2748584
Nat Struct Biol. 1994 Jun;1(6):399-409
7664054
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7547-52
15894609