The characteristics of molten globule states and folding pathways strongly depend on the sequence of a protein

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The majority of proteins perform their cellular function after folding into a specific and stable native structure. Additionally, for many proteins less compact ‘molten globule’ states have been observed. Current experimental observations show that the molten globule state can show varying degrees of compactness and solvent accessibility; the underlying molecular cause for this variation is not well understood. While the specificity of protein folding can be studied using protein lattice models, current design procedures for these models tend to generate sequences without molten globule-like behaviour. Here we alter the design process so the distance between the molten globule ensemble and the native structure can be steered; this allows us to design protein sequences with a wide range of folding pathways, and sequences with well-defined heat-induced molten globules. Simulating these sequences we find that (1) molten globule states are compact, but have less specific configurations compared to the folded state, (2) the nature of the molten globule state is highly sequence dependent, (3) both two-state and multi-state folding proteins may show heat-induced molten globule states, as observed in heat capacity curves. The varying nature of the molten globules and typical heat capacity curves associated with the transitions closely resemble experimental observations.

LanguageEnglish
Pages3173-3180
Number of pages8
JournalMolecular Physics
Volume116
Issue number21-22
DOIs
Publication statusPublished - 17 Nov 2018

Fingerprint

globules
folding
Molten materials
Hot Temperature
proteins
Protein Folding
Proteins
Protein folding
Specific heat
specific heat
heat
void ratio
curves
causes

Keywords

  • heat capacity
  • lattice model
  • Molten globule
  • multi-state folders
  • protein folding

Cite this

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title = "The characteristics of molten globule states and folding pathways strongly depend on the sequence of a protein",
abstract = "The majority of proteins perform their cellular function after folding into a specific and stable native structure. Additionally, for many proteins less compact ‘molten globule’ states have been observed. Current experimental observations show that the molten globule state can show varying degrees of compactness and solvent accessibility; the underlying molecular cause for this variation is not well understood. While the specificity of protein folding can be studied using protein lattice models, current design procedures for these models tend to generate sequences without molten globule-like behaviour. Here we alter the design process so the distance between the molten globule ensemble and the native structure can be steered; this allows us to design protein sequences with a wide range of folding pathways, and sequences with well-defined heat-induced molten globules. Simulating these sequences we find that (1) molten globule states are compact, but have less specific configurations compared to the folded state, (2) the nature of the molten globule state is highly sequence dependent, (3) both two-state and multi-state folding proteins may show heat-induced molten globule states, as observed in heat capacity curves. The varying nature of the molten globules and typical heat capacity curves associated with the transitions closely resemble experimental observations.",
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The characteristics of molten globule states and folding pathways strongly depend on the sequence of a protein. / Dijkstra, M. J.J.; Fokkink, W. J.; Heringa, J.; van Dijk, E.; Abeln, S.

In: Molecular Physics, Vol. 116, No. 21-22, 17.11.2018, p. 3173-3180.

Research output: Contribution to JournalArticleAcademicpeer-review

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