Three-dimensional computation of atom depth in complex molecular structures

Varrazzo, Daniele; Bernini, Andrea; Spiga, Ottavia; Ciutti, Arianna; Chiellini, S.; Venditti, Vincenzo; Bracci, Luisa; Niccolai, Neri

doi:10.1093/bioinformatics/bti444

Cited by 51 publications

(58 citation statements)

References 24 publications

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“…The A i values can be compared to the atomicdepth index (D i ), which is a quantitative description of the proximity of an atom to the molecular surface. [50] The tempolinduced attenuation pattern for the free RNA correlates well with the previously determined structure. [9] The greatest signal attenuation is observed for the 5' and 3' termini of the RNA and for the apical tetraloop, which are the most solvent accessible and dynamic regions of the molecule (data not shown).…”

Section: Resultssupporting

confidence: 76%

“…[71] The 3D atom depths, reported as depth indexes, D i , were calculated by using the SADIC software [50] for all aromatic carbon atoms analyzed by NMR spectroscopy. D i is defined according to Equa-tion (3), in which V i,r is the exposed volume of a sphere of radius r (sampling radius) centered on atom i, and V 0,r is the total volume of the same sphere.…”

Section: à2mentioning

confidence: 99%

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Guanidinoneomycin B Recognition of an HIV‐1 RNA Helix

et al. 2007

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Aminoglycoside antibiotics are small-molecule drugs that bind RNA. The affinity and specificity of aminoglycoside binding to RNA can be increased through chemical modification, such as guanidinylation. Here, we report the binding of guanidinoneomycin B (GNB) to an RNA helix from the HIV-1 frameshift site. The binding of GNB increases the melting temperature (T(m)) of the frameshift-site RNA by at least 10 degrees C, to a point at which a melting transition is not even observed in 2 M urea. A structure of the complex was obtained by using multidimensional heteronuclear NMR spectroscopic methods. We also used a novel paramagnetic-probe assay to identify the site of GNB binding to the surface of the RNA. GNB makes major-groove contacts to two sets of Watson-Crick bases and is in van der Waals contact with a highly structured ACAA tetraloop. Rings I and II of GNB fit into the major groove and form the binding interface with the RNA, whereas rings III and IV are exposed to the solvent and disordered. The binding of GNB causes a broadening of the major groove across the binding site.

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Section: Resultssupporting

confidence: 76%

Section: à2mentioning

confidence: 99%

Guanidinoneomycin B Recognition of an HIV‐1 RNA Helix

et al. 2007

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“…Our study is in general agreement with these findings using entirely different methods and parameters. Another method was reported to more fully express the 3-D character of the atom-depth measure by also taking into account the overall size and shape of the protein (Varrazzo et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Concentration of Specific Amino Acids at the Catalytic/Active Centers of Highly-Conserved “Housekeeping” Enzymes of Central Metabolism in Archaea, Bacteria and Eukaryota: Is There a Widely Conserved Chemical Signal of Prebiotic Assembly?

Pollack

Pan

Pearl

2010

Orig Life Evol Biosph

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In alignments of 1969 protein sequences the amino acid glycine and others were found concentrated at most-conserved sites within approximately 15 A of catalytic/active centers (C/AC) of highly conserved kinases, dehydrogenases or lyases of Archaea, Bacteria and Eukaryota. Lysine and glutamic acid were concentrated at least-conserved sites furthest from their C/ACs. Logistic-regression analyses corroborated the "movement" of glycine towards and lysine away from their C/ACs: the odds of a glycine occupying a site were decreased by 19%, while the odds for a lysine were increased by 53%, for every 10 A moving away from the C/AC. Average conservation of MSA consensus sites was highest surrounding the C/AC and directly decreased in transition toward model's peripheries. Findings held with statistical confidence using sequences restricted to individual Domains or enzyme classes or to both. Our data describe variability in the rate of mutation and likelihoods for phylogenetic trees based on protein sequence data and endorse the extension of substitution models by incorporating data on conservation and distance to C/ACs rather than only using cumulative levels. The data support the view that in the most-conserved environment immediately surrounding the C/AC of taxonomically distant and highly conserved essential enzymes of central metabolism there are amino acids whose identity and degree of occupancy is similar to a proposed amino acid set and frequency associated with prebiotic evolution.

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“…We note that the correlations in the solvent can extend up to a distance of 10 Å away from the protein surface. 19,20 To differentiate the relative importance of the bulk versus the local protein environment, we display the characteristic properties of the residues as a function of the depth index, d. 21 This index is defined as twice the ratio of the accessible volume of an atom V a to the exposed volume of an isolated atom V 0 ,…”

Section: Methodsmentioning

confidence: 99%

Depth dependent dynamics in the hydration shell of a protein

Servantie

Atılgan

2010

The Journal of Chemical Physics

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We study the dynamics of hydration water/protein association in folded proteins using lysozyme and myoglobin as examples. Extensive molecular dynamics simulations are performed to identify underlying mechanisms of the dynamical transition that corresponds to the onset of amplified atomic fluctuations in proteins. The results indicate that the number of water molecules within a cutoff distance of each residue scales linearly with protein depth index and is not affected by the local dynamics of the backbone. Keeping track of the water molecules within the cutoff sphere, we observe an effective residence time, scaling inversely with depth index at physiological temperatures while the diffusive escape is highly reduced below the transition. A depth independent orientational memory loss is obtained for the average dipole vector of the water molecules within the sphere when the protein is functional. While below the transition temperature, the solvent is in a glassy state, acting as a solid crust around the protein, inhibiting any large scale conformational fluctuations. At the transition, most of the hydration shell unfreezes and water molecules collectively make the protein more flexible.

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Three-dimensional computation of atom depth in complex molecular structures

Abstract: http://www.Sienabiogzefix.com/publication.

Cited by 51 publications

References 24 publications

Guanidinoneomycin B Recognition of an HIV‐1 RNA Helix

Guanidinoneomycin B Recognition of an HIV‐1 RNA Helix

Concentration of Specific Amino Acids at the Catalytic/Active Centers of Highly-Conserved “Housekeeping” Enzymes of Central Metabolism in Archaea, Bacteria and Eukaryota: Is There a Widely Conserved Chemical Signal of Prebiotic Assembly?

Depth dependent dynamics in the hydration shell of a protein

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