Local Secondary Structure Content Predicts Folding Rates for Simple, Two-state Proteins

Gong, Haipeng; Isom, Daniel G.; Srinivasan, R.; Rose, George D.

doi:10.1016/s0022-2836(03)00211-0

Cited by 108 publications

(112 citation statements)

References 35 publications

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“…Presumably then, the molten globule also is robust to changes in sequence. Additionally, it has been shown that the fraction of the protein involved in local hydrogen-bonded scaffold elements, ␣-helices, ␤-hairpins, and ␤-turns, is highly correlated with the folding rate: the larger this fraction, the faster the protein folds (102). This correlation implies that formation of the molten globule is unlikely to be a slow step in folding.…”

Section: What Anfinsen Could Not Have Knownmentioning

confidence: 99%

A backbone-based theory of protein folding

Rose

Fleming

Banavar

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

457

412

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Under physiological conditions, a protein undergoes a spontaneous disorder º order transition called "folding." The protein polymer is highly flexible when unfolded but adopts its unique native, three-dimensional structure when folded. Current experimental knowledge comes primarily from thermodynamic measurements in solution or the structures of individual molecules, elucidated by either x-ray crystallography or NMR spectroscopy. From the former, we know the enthalpy, entropy, and free energy differences between the folded and unfolded forms of hundreds of proteins under a variety of solvent͞cosolvent conditions. From the latter, we know the structures of Ϸ35,000 proteins, which are built on scaffolds of hydrogen-bonded structural elements, ␣-helix and ␤-sheet. Anfinsen showed that the amino acid sequence alone is sufficient to determine a protein's structure, but the molecular mechanism responsible for self-assembly remains an open question, probably the most fundamental open question in biochemistry. This perspective is a hybrid: partly review, partly proposal. First, we summarize key ideas regarding protein folding developed over the past half-century and culminating in the current mindset. In this view, the energetics of side-chain interactions dominate the folding process, driving the chain to self-organize under folding conditions. Next, having taken stock, we propose an alternative model that inverts the prevailing side-chain͞backbone paradigm. Here, the energetics of backbone hydrogen bonds dominate the folding process, with preorganization in the unfolded state. Then, under folding conditions, the resultant fold is selected from a limited repertoire of structural possibilities, each corresponding to a distinct hydrogen-bonded arrangement of ␣-helices and͞or strands of ␤-sheet.

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Section: What Anfinsen Could Not Have Knownmentioning

confidence: 99%

A backbone-based theory of protein folding

Rose

Fleming

Banavar

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

457

412

View full text Add to dashboard Cite

show abstract

“…[However, examining a whole set of proteins studied up to now, we saw that the reported equation, which works well for the two-state proteins (8), is much worse at predicting folding rates of multistate proteins and short peptides. ]…”

mentioning

confidence: 98%

“…It has been noticed that a high helical content is the main structural feature that decreases the contact order and accelerates folding of two-state proteins (7), and, for this group of proteins, a folding rate prediction method based on the content of secondary structure in their 3D structures has been suggested recently (8).…”

mentioning

confidence: 99%

Prediction of protein folding rates from the amino acid sequence-predicted secondary structure

Ivankov

Finkelstein

2004

Proc. Natl. Acad. Sci. U.S.A.

182

215

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“…Baker's group made an important observation in 1998 that the folding rates of twostate folding proteins correlate with the native topologies and proposed a concept of contact order (CO) (Plaxco et al 1998a) to predict the protein folding rates. Since then, a great deal of studies Fiebig and Dill 1993;Plaxco and Baker 1998b;Alm and Baker 1999;Debe and Goddard 1999;Mounoz and Eaton 1999;Dinner and Karplus 2001;Gromiha and Selvaraj 2001;Mirny and Shakhnovich 2001;Zhou and Zhou 2002;Gong et al 2003;Ivankov et al 2003;Nölting et al 2003;Zhang et al 2003;Ivankov and Finkelstein 2004) has shown that the protein folding rates correlated significantly with protein's three-dimensional or secondary structures. However, these conclusions are all based on the knowledge of the native structure of proteins.…”

Section: Introductionmentioning

confidence: 99%

The influence of protein coding sequences on protein folding rates of all-β proteins

Li¹,

Liang²

2011

gpb

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Abstract. It is currently believed that the protein folding rate is related to the protein structures and its amino acid sequence. However, few studies have been done on the problem that whether the protein folding rate is influenced by its corresponding mRNA sequence. In this paper, we analyzed the possible relationship between the protein folding rates and the corresponding mRNA sequences. The content of guanine and cytosine (GC content) of palindromes in protein coding sequence was introduced as a new parameter and added in the Gromiha's model of predicting protein folding rates to inspect its effect in protein folding process. The multiple linear regression analysis and jackknife test show that the new parameter is significant. The linear correlation coefficient between the experimental and the predicted values of the protein folding rates increased significantly from 0.96 to 0.99, and the population variance decreased from 0.50 to 0.24 compared with Gromiha's results. The results show that the GC content of palindromes in the corresponding protein coding sequence really influences the protein folding rate. Further analysis indicates that this kind of effect mostly comes from the synonymous codon usage and from the information of palindrome structure itself, but not from the translation information from codons to amino acids.Key words: All-β protein -Protein folding rate -Protein coding sequence -GC content of palindromes -Synonymous codon usage Abbreviations: GC content, guanine and cytosine content of protein coding sequence; P GC , GC content of palindromes; C GC , GC content of protein coding sequence.

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Local Secondary Structure Content Predicts Folding Rates for Simple, Two-state Proteins

Cited by 108 publications

References 35 publications

A backbone-based theory of protein folding

A backbone-based theory of protein folding

Prediction of protein folding rates from the amino acid sequence-predicted secondary structure

The influence of protein coding sequences on protein folding rates of all-β proteins

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