Rates of Peptide Folding

AP A5(A3RA)3A

Ref: Lednev I. K. et al. J. Am. Chem. Soc. 1999, 121, 8074-8086.

A 21 amino acid, mainly alanine, α-helical peptide (AP). The folding/unfolding activating barriers based on an nanosecond UV resonance Raman study. ~8 kcal/mol activation barrier; reciprocal rate constant ~240±60 ns at 37 °C (310 K).

Strand

Helix

??

Direct comparison to experiment

!00 ns simulation

Coil

_

-Shee t

_

-Bridge Bend Turn

_

-he lix 5-He lix 3-He lixCo il

_

-Shee t

_

-Bridge Bend Turn

_

-he lix 5-He lix 3-He lix

AP A5(A3RA)3A

Folding ~240±60 ns at 37 °C (310 K).

Force field: GROMOS 45A3Code: GROMACS 3.2.1.Solvent: SPC water.Box: PeriodicPressure: 1atmTemp: 310 K (Berendsen thermostat)Time step: 4fs (H atoms replaced by dummy atoms)

N-ter

C-ter

0 ns (starting structure)

N-ter

C-ter

10 ns

N-ter

C-ter

30 ns

C-ter

N-ter

50 ns

N-ter

C-ter

75 ns

N-ter

C-ter

70 ns

N-terC-ter

80 ns

N-ter C-ter

85 ns

N-ter

C-ter

100 ns

Curr. Opin. Struct. Biol. 2004, 14, 76-88

GB1SES

AP

YGGYGA

Experimental Folding rates

Helical: From native state

AP 0.8 μs

YGA 2.0 μs

YGG 0.7 μs

Helical: From liner/coil

YGG 0.7 μs

AP 0.8 μs

YGA 2.0 μs

Hairpin: From native state

GB1 6 μs

SES 0.8 μs

Hairpin: From liner/coil

GB1 6μs

SES 0.8μs