Amino Acid Network for the Discrimination of Native Protein Structures from Decoys

<div><p>Chemical cross-linking/Mass Spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues, which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms. Here, a force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. The force-field can be easily incorporated into current modeling methods and software. In this work, the force-field was implemented within the Rosetta ab initio relax protocol. We show a significant improvement in the quality of the models obtained relative to current strategies for constraint representation. This force-field contributes to the long-desired goal of obtaining the tertiary structures of proteins using XLMS data. Force-field parameters and usage instructions are freely available at http://m3g.iqm.unicamp.br/topolink/xlff <br></p></div><p></p><p></p>

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Network properties of decoys and CASP predicted models: a comparison with native protein structures

Molecular BioSystems ◽

10.1039/c3mb70157c ◽

2013 ◽

Vol 9 (7) ◽

pp. 1774 ◽

Cited By ~ 11

Author(s):

S. Chatterjee ◽

S. Ghosh ◽

S. Vishveshwara

Keyword(s):

Protein Structures ◽

Native Protein ◽

Network Properties

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Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen

Biochemical Journal ◽

10.1042/bj20040842 ◽

2004 ◽

Vol 385 (1) ◽

pp. 319-327 ◽

Cited By ~ 36

Author(s):

Regina WICHE ◽

Michaela GUBESCH ◽

Herbert KÖNIG ◽

Kay FÖTISCH ◽

Andreas HOFFMANN ◽

...

Keyword(s):

Food Allergy ◽

Amino Acid ◽

Prunus Avium ◽

Protein Structures ◽

Cross Reactivity ◽

Type I ◽

Binding Region ◽

Leukaemia Cell Line ◽

Bet V 1 ◽

Ige Binding

Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called ‘P-loop’ region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy.

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In-silicoprediction and modeling of theEntamoeba histolyticaproteins: Serine-richEntamoeba histolyticaprotein and 29 kDa Cysteine-rich protease

PeerJ ◽

10.7717/peerj.3160 ◽

2017 ◽

Vol 5 ◽

pp. e3160 ◽

Cited By ~ 5

Author(s):

Kumar Manochitra ◽

Subhash Chandra Parija

Keyword(s):

Amino Acid ◽

Structure Prediction ◽

Tertiary Structure ◽

Protein Structures ◽

Amino Acid Sequences ◽

Treatment Modalities ◽

Bioinformatic Tools ◽

Complex Protein ◽

A Cell ◽

Quaternary Structures

BackgroundAmoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings. There exists an ambiguity in the diagnosis of amoebiasis, and hence there arises a necessity for a better diagnostic approach. Serine-richEntamoeba histolyticaprotein (SREHP), peroxiredoxin and Gal/GalNAc lectin are pivotal inE. histolyticavirulence and are extensively studied as diagnostic and vaccine targets. For elucidating the cellular function of these proteins, details regarding their respective quaternary structures are essential. However, studies in this aspect are scant. Hence, this study was carried out to predict the structure of these target proteins and characterize them structurally as well as functionally using appropriatein-silicomethods.MethodsThe amino acid sequences of the proteins were retrieved from National Centre for Biotechnology Information database and aligned using ClustalW. Bioinformatic tools were employed in the secondary structure and tertiary structure prediction. The predicted structure was validated, and final refinement was carried out.ResultsThe protein structures predicted by i-TASSER were found to be more accurate than Phyre2 based on the validation using SAVES server. The prediction suggests SREHP to be an extracellular protein, peroxiredoxin a peripheral membrane protein while Gal/GalNAc lectin was found to be a cell-wall protein. Signal peptides were found in the amino-acid sequences of SREHP and Gal/GalNAc lectin, whereas they were not present in the peroxiredoxin sequence. Gal/GalNAc lectin showed better antigenicity than the other two proteins studied. All the three proteins exhibited similarity in their structures and were mostly composed of loops.DiscussionThe structures of SREHP and peroxiredoxin were predicted successfully, while the structure of Gal/GalNAc lectin could not be predicted as it was a complex protein composed of sub-units. Also, this protein showed less similarity with the available structural homologs. The quaternary structures of SREHP and peroxiredoxin predicted from this study would provide better structural and functional insights into these proteins and may aid in development of newer diagnostic assays or enhancement of the available treatment modalities.

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A Generic Force Field for Simulating Native Protein Structures Using Dissipative Particle Dynamics

Soft Matter ◽

10.1039/d1sm01194d ◽

2021 ◽

Author(s):

Rakesh K Vaiwala ◽

Ganapathy Ayappa

Keyword(s):

Molecular Dynamics ◽

Force Field ◽

Molecular Dynamics Simulations ◽

Dissipative Particle Dynamics ◽

Protein Structures ◽

Particle Dynamics ◽

Coarse Grained ◽

Native Protein ◽

Dynamics Simulations

A coarse-grained force field for molecular dynamics simulations of native structures of proteins in a dissipative particle dynamics (DPD) framework is developed. The parameters for bonded interactions are derived by...

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