Rates of Peptide Folding

1
Rates of Peptide Folding
2
AP A5(A3RA)3A
Ref Lednev I. K. et al. J. Am. Chem. Soc. 1999,
121, 8074-8086.

• A 21 amino acid, mainly alanine, a-helical
  peptide (AP).
• The folding/unfolding activating barriers based
  on an nanosecond UV resonance Raman study.
• 8 kcal/mol activation barrier reciprocal rate
  constant 24060 ns at 37 C (310 K).

Strand
?
Helix
Direct comparison to experiment
3
AP A5(A3RA)3A
Folding 24060 ns at 37 C (310 K).
!00 ns simulation
Force field GROMOS 45A3 Code GROMACS
3.2.1. Solvent SPC water. Box Periodic Pressu
re 1atm Temp 310 K (Berendsen thermostat) Time
step 4fs (H atoms replaced by dummy atoms)
4
C-ter
N-ter
N-ter
N-ter
C-ter
N-ter
C-ter
30 ns
50 ns
C-ter
10 ns
0 ns (starting structure)
N-ter
C-ter
N-ter
N-ter
C-ter
C-ter
C-ter
N-ter
N-ter
C-ter
85 ns
75 ns
70 ns
80 ns
100 ns
5
Experimental Folding rates
YGA
YGG
AP
GB1
SES
Curr. Opin. Struct. Biol. 2004, 14, 76-88
6
Helical From native state
YGA 2.0 µs
YGG 0.7 µs
AP 0.8 µs
7
Helical From liner/coil
YGA 2.0 µs
YGG 0.7 µs
AP 0.8 µs
8
Hairpin From native state
GB1 6 µs
SES 0.8 µs
9
Hairpin From liner/coil
GB1 6µs
SES 0.8µs