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Helix nucleation kinetics from molecular simulations in explicit solvent
Author(s) -
Hummer Gerhard,
García Angel E.,
Garde Shekhar
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20010101)42:1<77::aid-prot80>3.0.co;2-#
Subject(s) - nucleation , helix (gastropod) , chemistry , molecular dynamics , protein folding , temperature jump , arrhenius equation , crystallography , folding (dsp implementation) , chemical physics , thermodynamics , alpha helix , kinetics , activation energy , computational chemistry , circular dichroism , physics , ecology , biochemistry , organic chemistry , quantum mechanics , snail , electrical engineering , biology , engineering
We study the reversible folding/unfolding of short Ala and Gly‐based peptides by molecular dynamics simulations of all‐atom models in explicit water solvent. A kinetic analysis shows that the formation of a first α‐helical turn occurs within 0.1–1 ns, in agreement with the analyses of laser temperature jump experiments. The unfolding times exhibit Arrhenius temperature dependence. For a rapidly nucleating all‐Ala peptide, the helix nucleation time depends only weakly on temperature. For a peptide with enthalpically competing turn‐like structures, helix nucleation exhibits an Arrhenius temperature dependence, corresponding to the unfolding of enthalpic traps in the coil ensemble. An analysis of structures in a “transition‐state ensemble” shows that helix‐to‐coil transitions occur predominantly through breaking of hydrogen bonds at the helix ends, particularly at the C‐terminus. The temperature dependence of the transition‐state ensemble and the corresponding folding/unfolding pathways illustrate that folding mechanisms can change with temperature, possibly complicating the interpretation of high‐temperature unfolding simulations. The timescale of helix formation is an essential factor in molecular models of protein folding. The rapid helix nucleation observed here suggests that transient helices form early in the folding event. Proteins 2001;42:77–84. © 2000 Wiley‐Liss, Inc.