Compact units in proteins

Zehfus, Michael; Rose, George D.

doi:10.1021/bi00367a062

Cited by 98 publications

(49 citation statements)

References 26 publications

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“…Therefore, proteolytic enzymes may be used as reliable probes of protein structure, dynamics, and folding pathways. Furthermore, the consistency with the experimental cleavages appears to provide a validation of the building block folding model, where the independently folding hydrophobic units are obtained through hierarchical assembly of these conformationally fluctuating building blocks [109,110]. As a result, this model is in line with the proposal that protein folding is a hierarchical event [111,112], where parts constituting local minima of energy fold first, with their subsequent association and mutual stabilization to finally yield the global fold.…”

Section: Molecular Dynamics Simulationssupporting

confidence: 70%

Recent developments in structural proteomics for protein structure determination

Liu

Hsu

2005

Proteomics

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The major challenges in structural proteomics include identifying all the proteins on the genome-wide scale, determining their structure-function relationships, and outlining the precise three-dimensional structures of the proteins. Protein structures are typically determined by experimental approaches such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. However, the knowledge of three-dimensional space by these techniques is still limited. Thus, computational methods such as comparative and de novo approaches and molecular dynamic simulations are intensively used as alternative tools to predict the three-dimensional structures and dynamic behavior of proteins. This review summarizes recent developments in structural proteomics for protein structure determination; including instrumental methods such as X-ray crystallography and NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulations.

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Section: Molecular Dynamics Simulationssupporting

confidence: 70%

Recent developments in structural proteomics for protein structure determination

Liu

Hsu

2005

Proteomics

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“…Instead of trying exhaustively to calculate the compactness of each of these units, it is much more efficient to use a screening parameter to locate units that seem compact, and perform the compactness calculation only on these units. Because compact units are close to spherical in shape (Zehfus & Rose, 1986), spheres of varying sizes are moved through the protein's coordinates to find sets of residues that fit well within the spheres. These sets of residues are then used as seeds for further processing.…”

Section: Overview Of Unit Discovery Methodsmentioning

confidence: 99%

Identification of compact, hydrophobically stabilized domains and modules containing multiple peptide chains

Zehfus

1997

Protein Science

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Compactness has been used to locate discontinuous structural units containing one or more polypeptide chains in proteins of known structure. Rather than exhaustively calculating the compactness of all possible units, our procedure uses a screening algorithm to find discontinuous regions that are potentially compact. Precise calculations of compactness are restricted only to units in these regions. With our procedure, compactness can be used to discover discontinuous domains with virtually any number of disjoint peptides. Small, single-domain proteins may contain several compact regions: thus, compact regions do not always correspond to folding domains. Because a domain is an independent folding unit and should contain a hydrophobic core, compact units were further examined for the presence of hydrophobic clusters (Zehfus MH, 1995, Protein Sci 41188-1202). This added constraint limits the number of acceptable units and helps greatly in the location of the true structural domains. The larger hydrophobically stabilized compact units correspond to domains, while the smaller units may correspond to folding intermediates.Keywords: compact domains; compact units; discontinuous domains; domains; folding units; stabilized modules Ever since the first protein structure was elucidated by X-ray crystallography, it has been possible to locate distinct, spatially separable regions within many proteins that are thought to correspond to structural domains (Wetlaufer, 1973). While many domainfinding algorithms were developed in the late

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“…A candidate is assessed by a function based on four quantities: compactness, isolation, hydrophobicity, and segmentation. We use the definition proposed by Zehfus and Rose (1986) to calculate the compactness of a cut unit. The degree of isolation of a unit is based on the solvent accessible surface area (ASA) that was originally buried in the interior of the protein and is exposed to the solvent after cutting.…”

mentioning

confidence: 99%

Hydrophobic folding units derived from dissimilar monomer structures and their interactions

Tsai

Nussinov

1997

Protein Science

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We have designed an automated procedure to cut a protein into compact hydrophobic folding units. The hydrophobic units are large enough to contain tertiary non-local interactions, reflecting potential nucleation sites during protein folding. The quality of a hydrophobic folding unit is evaluated by four criteria. The first two correspond to visual characterization of a structural domain, namely, compactness and extent of isolation. We use the definition of Zehfus and Rose (Zehfus MH, Rose GD, 1986, Biochemistry 25:335-340) to calculate the compactness of a cut protein unit. The isolation of a unit is based on the solvent accessible surface area (ASA) originally buried in the interior and exposed to the solvent after cutting. The third quantity is the hydrophobicity, equivalent to the fraction of the buried non-poiar ASA with respect to the total non-polar ASA. The last criterion in the evaluation of a folding unit is the number of segments it includes. To conform with the rationale of obtaining hydrophobic units, which may relate to early folding events, the hydrophobic interactions are implicitly and explicitly applied in their generation and assessment. We follow Holm and Sander (Holm L, Sander C, 1994, Proteins 19:256-268) to reduce the multiple cutting-point problem to a one-dimensional search for all reasonable trial cuts. However, as here we focus on the hydrophobic cores, the contact matrix used to obtain the first non-trivial eigenvector contains only hydrophobic contacts, rather than all, hydrophobic and hydrophilic, interactions. This dataset of hydrophobic folding units, derived from structurally dissimilar single chain monomers, is particularly useful for investigations of the mechanism of protein folding. For cases where there are kinetic data, the one or more hydrophobic folding units generated for a protein correlate with the two or with the three-state folding process observed. We carry out extensive amino acid sequence order independent structural comparisons to generate a structurally non-redundant set of hydrophobic folding units for fold recognition and for statistical purposes.

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Compact units in proteins

Cited by 98 publications

References 26 publications

Recent developments in structural proteomics for protein structure determination

Recent developments in structural proteomics for protein structure determination

Identification of compact, hydrophobically stabilized domains and modules containing multiple peptide chains

Hydrophobic folding units derived from dissimilar monomer structures and their interactions

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