Relationships between unfolded configurations of proteins and dynamics of folding to the native state

Gürsoy, Attila; Keskin, Özlem; Türkay, Metin; Erman, Burak

doi:10.1002/polb.21018

Cited by 3 publications

(2 citation statements)

References 56 publications

(81 reference statements)

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“…For example, a recent study of molecular dynamics folding trajectories found that randomly generated chains folded more slowly and less efficiently than chains generated with native-like conformations determined by a knowledge-based potential. 31 This indicates that not all conformations in the unfolded state are equally likely to proceed to the folded state and that there may in fact be specific bottlenecks for leaving the unfolded basin. However, that study did not examine how realistic or probabilistic the productive unfolded conformations are.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, we believe this method of reweighting wormlike chain distributions to account for intrachain interactions is robust, realistic, and predictive and may be a useful starting point for further models of protein folding. For example, a recent study of molecular dynamics folding trajectories found that randomly generated chains folded more slowly and less efficiently than chains generated with native-like conformations determined by a knowledge-based potential . This indicates that not all conformations in the unfolded state are equally likely to proceed to the folded state and that there may in fact be specific bottlenecks for leaving the unfolded basin.…”

Section: Discussionmentioning

confidence: 99%

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A General Polymer Model of Unfolded Proteins under Folding Conditions

2010

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There is increasing evidence that a polypeptide chain in solvent conditions that favor folding may have transient structure and is significantly more compact than a fully denatured chain. However, there is no sequence-dependent model to capture such interactions. In this work, we present a simple and computationally inexpensive model based on a wormlike chain with excluded volume. The probability distribution of millions of such chains is reweighted to bias compact conformations in which residues of similar hydrophobicity are located near each other. This model, which has one adjustable parameter, is fit to measured values of intramolecular contact formation, which has been shown to be extremely sensitive to various models of intrachain distances. We show that under various denaturant concentrations, there is good convergence of the model for several different sequences with a wide range of dynamics. We also show that this model quantitatively predicts paramagnetic resonance enhancement (PRE) measurements with no adjustable parameters. Therefore a simple, probabilistic model that accounts for sequence-specific interactions may give a more realistic starting point for predictions of protein folding.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A General Polymer Model of Unfolded Proteins under Folding Conditions

2010

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Optimum folding pathways for growing protein chains

Senturk

Baday²,

Arkun³

et al. 2007

Phys. Biol.

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The folding of a protein is studied as it grows residue by residue from the N-terminus and enters an environment that stabilizes the folded state. This mode of folding of a growing chain is different from refolding where the full chain folds from a disordered initial configuration to the native state. We propose a sequential dynamic optimization method that computes the evolution of optimum folding pathways as amino acid residues are added to the peptide chain one by one. The dynamic optimization formulation is deterministic and uses Newton's equations of motion and a Go-type potential that establishes the native contacts and excluded volume effects. The method predicts the optimal energy-minimizing path among all the alternative feasible pathways. As two examples, the folding of the chicken villin headpiece, a 36-residue protein, and chymotrypsin inhibitor 2 (CI2), a 64-residue protein, are studied. Results on the villin headpiece show significant differences from the refolding of the same chain studied previously. Results on CI2 mostly agree with the results of refolding experiments and computational work.

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Predicting three-dimensional structure of protein fragments from dihedral angle propensities and molecular dynamics

Blayney¹,

Ojha²,

Shapcott³

2010

IJCBDD

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Incorporating the existing knowledge of protein structural preferences, e.g., amino acid angle frequencies, in structure prediction have proven to be less successful with smaller peptides. In this work, we compare the effectiveness of backbone angle propensity libraries derived from two protein data sets: one consisting of proteins of unrestricted lengths; the second containing proteins ranging in size from 40 to 75 residues. Model structures for 29 target peptides are predicted using a threading algorithm and their stability evaluated using in vacuo molecular dynamics simulations. Structures derived from the data set consisting of smaller proteins outperformed those developed from that unrestricted by protein length.

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Relationships between unfolded configurations of proteins and dynamics of folding to the native state

Cited by 3 publications

References 56 publications

A General Polymer Model of Unfolded Proteins under Folding Conditions

A General Polymer Model of Unfolded Proteins under Folding Conditions

Optimum folding pathways for growing protein chains

Predicting three-dimensional structure of protein fragments from dihedral angle propensities and molecular dynamics

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