Mechanism of protein folding

Nölting, Bengt; Andert, Karl

doi:10.1002/1097-0134(20001115)41:3<288::aid-prot20>3.0.co;2-c

Cited by 65 publications

(60 citation statements)

References 82 publications

(78 reference statements)

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“…Of the dimers we simulated, experimental F values are currently available only for Arc-repressor. 46,49 The histograms of the computed and experimental F values for Arc-repressor satisfactorily overlap. Both histograms indicate a partially structured transition state; however, the computed F values are generally higher than those from experiment.…”

Section: Coupled Folding-binding Reactionsmentioning

confidence: 99%

“…While F value analysis has been widely used to decipher folding mechanisms, there are only few cases where F value analysis has been applied to characterize the TSE of binding. [46][47][48][49][50] To study the nature of the binding transition state ensemble and its dependence on the degree of flexibility, we have simulated the association of various monomeric proteins into dimers, trimers, and tetramers. The protein complexes we have selected differ in their size, topology, and detailed association mechanism.…”

Section: Introductionmentioning

confidence: 99%

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A Survey of Flexible Protein Binding Mechanisms and their Transition States Using Native Topology Based Energy Landscapes

Levy

Cho

Onuchic

et al. 2005

Journal of Molecular Biology

214

246

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Section: Coupled Folding-binding Reactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Survey of Flexible Protein Binding Mechanisms and their Transition States Using Native Topology Based Energy Landscapes

Levy

Cho

Onuchic

et al. 2005

Journal of Molecular Biology

214

246

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“…For this reason the nucleation mechanism is typically considered the most common folding mechanism among small two-state proteins. 25 A few years ago, Sánchez and Kiefhaber reported a set of experimental data indicative that -values are considerably inaccurate unless the difference in the folding free energy upon mutation is larger than 7 kJ/mol. 26 A refute by Fersht followed based on the premise that the 7 kJ/mol cutoff was based on mutations that are unsuitable for -value analysis because they are disruptive.…”

Section: Introductionmentioning

confidence: 99%

Identifying critical residues in protein folding: Insights from ϕ-value and Pfold analysis

Faísca

Travasso

Ball

et al. 2008

The Journal of Chemical Physics

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We apply a simulational proxy of the -value analysis and perform extensive mutagenesis experiments to identify the nucleating residues in the folding "reactions" of two small lattice Gō polymers with different native geometries. Our findings show that for the more complex native fold ͑i.e., the one that is rich in nonlocal, long-range bonds͒, mutation of the residues that form the folding nucleus leads to a considerably larger increase in the folding time than the corresponding mutations in the geometry that is predominantly local. These results are compared to data obtained from an accurate analysis based on the reaction coordinate folding probability P fold and on structural clustering methods. Our study reveals a complex picture of the transition state ensemble. For both protein models, the transition state ensemble is rather heterogeneous and splits up into structurally different populations. For the more complex geometry the identified subpopulations are actually structurally disjoint. For the less complex native geometry we found a broad transition state with microscopic heterogeneity. These findings suggest that the existence of multiple transition state structures may be linked to the geometric complexity of the native fold. For both geometries, the identification of the folding nucleus via the P fold analysis agrees with the identification of the folding nucleus carried out with the -value analysis. For the most complex geometry, however, the applied methodologies give more consistent results than for the more local geometry. The study of the transition state structure reveals that the nucleus residues are not necessarily fully native in the transition state. Indeed, it is only for the more complex geometry that two of the five critical residues show a considerably high probability of having all its native bonds formed in the transition state. Therefore, one concludes that, in general, the -value correlates with the acceleration/deceleration of folding induced by mutation, rather than with the degree of nativeness of the transition state, and that the "traditional" interpretation of -values may provide a more realistic picture of the structure of the transition state only for more complex native geometries.

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“…Second, the order of appearance of contacts was not considered, even though much is known about folding pathways. [15][16][17][18] In the new approach, we tried to incorporate "physicality" and protein-like characteristics by using protein templates and simple rules. The rules consist of common sense facts for packing of secondary structures.…”

Section: Introductionmentioning

confidence: 99%

“…Rules for the order of appearance were derived from the general assumptions of a nucleation/ propagation pathway. 15 …”

Section: Introductionmentioning

confidence: 99%

Predicting interresidue contacts using templates and pathways

Shao

Bystroff

2003

Proteins

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We present a novel method, HMMSTR-CM, for protein contact map predictions. Contact potentials were calculated by using HMMSTR, a hidden Markov model for local sequence structure correlations. Targets were aligned against protein templates using a Bayesian method, and contact maps were generated by using these alignments. Contact potentials then were used to evaluate these templates. An ab initio method based on the target contact potentials using a rule-based strategy to model the protein-folding pathway was developed. Fold recognition and ab initio methods were combined to produce accurate, protein-like contact maps. Pathways sometimes led to an unambiguous prediction of topology, even without using templates. The results on CASP5 targets are discussed. Also included is a brief update on the quality of fully automated ab initio predictions using the I-sites server. Proteins 2003;53:497-502.

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Mechanism of protein folding

Cited by 65 publications

References 82 publications

A Survey of Flexible Protein Binding Mechanisms and their Transition States Using Native Topology Based Energy Landscapes

A Survey of Flexible Protein Binding Mechanisms and their Transition States Using Native Topology Based Energy Landscapes

Identifying critical residues in protein folding: Insights from ϕ-value and Pfold analysis

Predicting interresidue contacts using templates and pathways

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