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Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution

A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as...

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Autores principales: Nicolau Jr., Dan V., Paszek, Ewa, Fulga, Florin, Nicolau, Dan V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252106/
https://www.ncbi.nlm.nih.gov/pubmed/25462574
http://dx.doi.org/10.1371/journal.pone.0114042
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author Nicolau Jr., Dan V.
Paszek, Ewa
Fulga, Florin
Nicolau, Dan V.
author_facet Nicolau Jr., Dan V.
Paszek, Ewa
Fulga, Florin
Nicolau, Dan V.
author_sort Nicolau Jr., Dan V.
collection PubMed
description A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 Å, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced “leopard skin”-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism.
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spelling pubmed-42521062014-12-05 Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution Nicolau Jr., Dan V. Paszek, Ewa Fulga, Florin Nicolau, Dan V. PLoS One Research Article A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 Å, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced “leopard skin”-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism. Public Library of Science 2014-12-02 /pmc/articles/PMC4252106/ /pubmed/25462574 http://dx.doi.org/10.1371/journal.pone.0114042 Text en © 2014 Nicolau Jr http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nicolau Jr., Dan V.
Paszek, Ewa
Fulga, Florin
Nicolau, Dan V.
Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title_full Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title_fullStr Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title_full_unstemmed Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title_short Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution
title_sort mapping hydrophobicity on the protein molecular surface at atom-level resolution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252106/
https://www.ncbi.nlm.nih.gov/pubmed/25462574
http://dx.doi.org/10.1371/journal.pone.0114042
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