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Literature DB >> 12496119

Direct molecular dynamics observation of protein folding transition state ensemble.

Feng Ding¹, Nikolay V Dokholyan, Sergey V Buldyrev, H Eugene Stanley, Eugene I Shakhnovich.

Abstract

The concept of the protein transition state ensemble (TSE), a collection of the conformations that have 50% probability to convert rapidly to the folded state and 50% chance to rapidly unfold, constitutes the basis of the modern interpretation of protein engineering experiments. It has been conjectured that conformations constituting the TSE in many proteins are the expanded and distorted forms of the native state built around a specific folding nucleus. This view has been supported by a number of on-lattice and off-lattice simulations. Here we report a direct observation and characterization of the TSE by molecular dynamic folding simulations of the C-Src SH3 domain, a small protein that has been extensively studied experimentally. Our analysis reveals a set of key interactions between residues, conserved by evolution, that must be formed to enter the kinetic basin of attraction of the native state.

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Year: 2002 PMID： 12496119 PMCID： PMC1302427 DOI： 10.1016/S0006-3495(02)75352-6

Source DB: PubMed Journal: Biophys J ISSN： 0006-3495 Impact factor: 4.033

37 in total

Direct molecular dynamics observation of protein folding transition state ensemble.

1. Is protein unfolding the reverse of protein folding? A lattice simulation analysis.

2. A theoretical search for folding/unfolding nuclei in three-dimensional protein structures.

3. Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures.

Review 4. How do small single-domain proteins fold?

5. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution.

6. Obligatory steps in protein folding and the conformational diversity of the transition state.

7. Important role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain.

8. Discrete molecular dynamics studies of the folding of a protein-like model.

9. Molecular dynamics simulation of the unfolding of barnase: characterization of the major intermediate.

10. Contact order, transition state placement and the refolding rates of single domain proteins.

1. Posttransition state desolvation of the hydrophobic core of the src-SH3 protein domain.

2. Unfolding of globular proteins: monte carlo dynamics of a realistic reduced model.

3. Multiple folding pathways of the SH3 domain.

4. What can one learn from experiments about the elusive transition state?

5. A structural model of polyglutamine determined from a host-guest method combining experiments and landscape theory.

6. Trp zipper folding kinetics by molecular dynamics and temperature-jump spectroscopy.

7. Formation of the folding nucleus of an SH3 domain investigated by loosely coupled molecular dynamics simulations.

8. Molecular dynamics simulation of amyloid beta dimer formation.

9. Discrete molecular dynamics distinguishes nativelike binding poses from decoys in difficult targets.

10. Differences in the folding transition state of ubiquitin indicated by phi and psi analyses.