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Alfredo Colosimo

Publications and source records attributed to Alfredo Colosimo.

11 recordsLinked to original sources
PubMed2005

Functional essentiality from topology features in metabolic networks: a case study in yeast.

The relation between the position of mutations in Saccharomyces cerevisiae metabolic network and their lethality is the subject of this work. We represent the topology of the network by a directed graph: nodes are metabolites and arcs represent the reactions; a mutation corresponds to the removal of all the arcs referring to the deleted enzyme. Using publicly available knock-out data, we show that lethality corresponds to the lack of alternative paths in the perturbed network linking the nodes affected by the enzyme deletion. Such feature is at the basis of the recently recognized importance of 'marginal' arcs of metabolic networks.

Energy Metabolism↗
PubMed2005

Early events in protein aggregation: molecular flexibility and hydrophobicity/charge interaction in amyloid peptides as studied by molecular dynamics simulations.

In a previous article (Zbilut et al., Biophys J 2003;85:3544-3557), we demonstrated how an aggregation versus folding choice could be approached considering hydrophobicity distribution and charge. In this work, our aim is highlighting the mutual interaction of charge and hydrophobicity distribution in the aggregation process. Use was made of two different peptides, both derived from a transmembrane protein (amyloid precursor protein; APP), namely, Abeta(1-28) and Abeta(1-40). Abeta(1-28) has a much lower aggregation propensity than Abeta(1-40). The results obtained by means of molecular dynamics simulations show that, when submitted to the most "aggregation-prone" environment, corresponding to the isoelectric point and consequently to zero net charge, both peptides acquire their maximum flexibility, but Abeta(1-40) has a definitely higher conformational mobility than Abeta(1-28). The absence of a hydrophobic "tail," which is the most mobile part of the molecule in Abeta(1-40), is the element lacking in Abeta(1-28) for obtaining a "fully aggregating" phenotype. Our results suggest that conformational flexibility, determined by both hydrophobicity and charge effect, is the main mechanistic determinant of aggregation propensity.

Amyloid↗
PubMed2004

Temperature acclimation modulates the oxygen binding properties of the Atlantic cod (Gadus morhua L.) genotypes-HbI*1/1, HbI*1/2, and HbI*2/2-by changing the concentrations of their major hemoglobin components (results from growth studies at different temperatures).

The influence of long-term acclimation temperatures in Atlantic cod (Gadus morhua) was studied by growth experiments carried out over a total of 272 individuals. The attention focused on the structural and functional modulation of the five electrophoretically distinguishable genotypes of cod hemoglobin (HbI*1/1, HbI*1/2, HbI*2/2, HbI*1/2b, and HbI*2/2b) and on the correlation with body length/weight. The main results can be summarized as follows. (1) Acclimation to lower (4 and 8 degrees C) and higher (12 and 15 degrees C) temperatures favors the expression of, respectively, more anodic and more cathodic hemoglobin components. (2) The optimal O(2) transporting features are observed at 12 degrees C, as well as a saturation-dependent temperature dependence of O(2) binding, which furthermore is strongly dependent upon the acclimation background. (3) The optimal growth condition for the three main genotypes (HbI*1/1, HbI*1/2, and HbI*2/2) is associated with T=12 degrees C. The overall results are consistent with the idea that environmental temperatures constitute a primary factor in the aggregation of individuals physiologically more than genetically homogeneous. This is fully confirmed by careful statistical analysis carried out over a subset of individuals for which the full set of structural (isoelectric focusing), functional (O(2) binding), and growth data was available.

Acclimatization↗
PubMed2003

Otoacoustic emissions at different click intensities: invariant and subject-dependent features.

A study of click-evoked otoacoustic emissions (CEOAEs) elicited at stimulation intensities from 35 to >80 dB was carried out by recurrence quantification analysis on signals from both normal and hearing-impaired subjects. In normal subjects, a clear scaling of determinism with increasing stimulation intensity was observed in the click intensity range from 41 to 59 dB. Outside that range and, in particular, above its upper end, subject-dependent features appeared in the form of different maximal levels of determinism. A comparative analysis of responses from hearing-impaired subjects with conductive hearing losses and sensorineural hearing losses suggested that the principal contributor to this behavior is the middle ear and allowed us to discriminate the two pathologies solely on the basis of CEOAEs. These observations are consistent with a simple phenomenological model of the auditory periphery in which different functional modules are sequentially recruited at increasing stimulus intensities, with a consequent rise in CEOAE coherence.

Acoustic Stimulation↗
PubMed2003

Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40).

The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Abeta(1-40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation.

Acid Anhydride Hydrolases↗
PubMed2002

Molecular dynamics study of a hyperthermophilic and a mesophilic rubredoxin.

In recent years, increased interest in the origin of protein thermal stability has gained attention both for its possible role in understanding the forces governing the folding of a protein and for the design of new highly stable engineered biocatalysts. To study the origin of thermostability, we have performed molecular dynamics simulations of two rubredoxins, from the mesophile Clostridium pasteurianum and from the hyperthermophile Pyrococcus furiosus. The simulations were carried out at two temperatures, 300 and 373 K, for each molecule. The length of the simulations was within the range of 6-7.2 ns. The rubredoxin from the hyperthermophilic organism was more flexible than its mesophilic counterpart at both temperatures; however, the overall flexibility of both molecules at their optimal growth temperature was the same, despite 59% sequence homology. The conformational space sampled by both molecules was larger at 300 K than at 373 K. The essential dynamics analysis showed that the principal overall motions of the two molecules are significantly different. On the contrary, each molecule showed similar directions of motion at both temperatures.

Bacterial Proteins↗
PubMed2002

Comparison of transient otoacoustic emission responses from neonatal and adult ears.

Transient otoacoustic emission (TEOAE) responses from neonatal (age: 48 h) and adult subjects (age: 26.6 +/- 10.0 yr) were analyzed by the combined use of recurrence quantification analysis and singular value decomposition. The data from the two age groups showed significant differences and similarities. The neonatal responses presented less deterministic structures than those of the adults in terms of recurrent dynamic features. In both data sets, the same high level of individual specific dynamic features was observed. The results from the singular value decomposition analysis suggest that a large percentage of variability in all of the analyzed responses can be explained by four to five essential modes. This number is lower than that observed in simulated TEOAE responses generated by a five-component gammatone model. A possible explanation is presented, based on simple instrumental and morphoanatomic considerations.

Adult↗
PubMed2002

Review of nonlinear analysis of proteins through recurrence quantification.

This review considers the use of a nonlinear signal analysis tool, recurrence quantification analysis, as a method to study sequence/structure relationships of proteins. Four broad categories are discussed: (1) a point of view involving information contained in deterministic aspects of hydrophobicity; (2) the analysis of protein hydrophobicity "singularities"; (3) time-series analysis of protein dynamics simulations; and (4) prediction of protein secondary structure.

Algorithms↗
PubMedDate not supplied

Structure-related statistical singularities along protein sequences: a correlation study.

A data set composed of 1141 proteins representative of all eukaryotic protein sequences in the Swiss-Prot Protein Knowledge base was coded by seven physicochemical properties of amino acid residues. The resulting numerical profiles were submitted to correlation analysis after the application of a linear (simple mean) and a nonlinear (Recurrence Quantification Analysis, RQA) filter. The main RQA variables, Recurrence and Determinism, were subsequently analyzed by Principal Component Analysis. The RQA descriptors showed that (i) within protein sequences is embedded specific information neither present in the codes nor in the amino acid composition and (ii) the most sensitive code for detecting ordered recurrent (deterministic) patterns of residues in protein sequences is the Miyazawa-Jernigan hydrophobicity scale. The most deterministic proteins in terms of autocorrelation properties of primary structures were found (i) to be involved in protein-protein and protein-DNA interactions and (ii) to display a significantly higher proportion of structural disorder with respect to the average data set. A study of the scaling behavior of the average determinism with the setting parameters of RQA (embedding dimension and radius) allows for the identification of patterns of minimal length (six residues) as possible markers of zones specifically prone to inter- and intramolecular interactions.

Amino Acid Sequence↗
PubMedDate not supplied

Charge and hydrophobicity patterning along the sequence predicts the folding mechanism and aggregation of proteins: a computational approach.

The presence of partially folded intermediates along the folding funnel of proteins has been suggested to be a signature of potentially aggregating systems. Many studies have concluded that metastable, highly flexible intermediates are the basic elements of the aggregation process. In a previous paper, we demonstrated how the choice between aggregation and folding behavior was influenced by hydrophobicity distribution patterning along the sequence, as quantified by recurrence quantification analysis (RQA) of the Myiazawa-Jernigan coded primary structures. In the present paper, we tried to unify the "partially folded intermediate" and "hydrophobicity/charge" models of protein aggregation verifying the ability of an empirical relation, developed for rationalizing the effect of different mutations on aggregation propensity of acyl-phosphatase and based on the combination of hydrophobicity RQA and charge descriptors, to discriminate in a statistically significant way two different protein populations: (a) proteins that fold by a process passing by partially folded intermediates and (b) proteins that do not present partially folded intermediates.

Acid Anhydride Hydrolases↗