| Autor: |
Nicolau DV Jr; Department of Integrative Biology, University of California, Berkeley, California, United States of America., Paszek E; Department of Electrical Engineering & Electronics, University of Liverpool, Liverpool, United Kingdom., Fulga F; Department of Electrical Engineering & Electronics, University of Liverpool, Liverpool, United Kingdom., Nicolau DV; Department of Electrical Engineering & Electronics, University of Liverpool, Liverpool, United Kingdom; Department of Bioengineering, McGill University, Montreal, Quebec, Canada. |
| Jazyk: |
angličtina |
| Zdroj: |
PloS one [PLoS One] 2014 Dec 02; Vol. 9 (12), pp. e114042. Date of Electronic Publication: 2014 Dec 02 (Print Publication: 2014). |
| DOI: |
10.1371/journal.pone.0114042 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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