Biomedical subjects

Mauro Colafranceschi

Publications and source records attributed to Mauro Colafranceschi.

6 recordsLinked to original sources

PubMed2006

Dissecting drug and vehicle metabolic effects in rats by a metabonomic approach.

A combined application of high resolution (1)H NMR spectroscopy and multivariate statistical techniques focused on establishing a consistent statistical approach to metabonomic studies was tested. The data reduction, which is preliminary to the application of multivariate analysis to NMR spectra, was carried out by means of two complementary methods: pure Pattern Recognition (PR) and Assigned Signal Analysis (ASA). The simultaneous use of both approaches allowed us to obtain additional information in the analysis of metabonomic data, compared to the use of PR alone. This additional information consists in the possibility of a biochemical interpretation of the effects induced by treatment with xenobiotics, such as drugs or drug vehicles, on the metabolic networks of the systems under investigation. This approach allowed us to ascertain that a single-dose treatment with ST1959 vehicled by Sesame oil affects the production of hepatic glucose associated to an increment of the amino acid ketogenic process.

Algorithms↗

PubMed2006

Entropic criteria for protein folding derived from recurrences: six residues patch as the basic protein word.

Some research has suggested that patches of six constitute an important amino acid window length in proteins for conveying information. We present database evidence that supports this conjecture, as well as additional recurrence-based data that characterization and quantification of these words affect the folding/aggregation features of proteins. Other indirect evidence is presented and discussed.

Amino Acid Sequence↗

PubMed2003

Large contact surface interactions between proteins detected by time series analysis methods: case study on C-phycocyanins.

A purely sequence-dependent approach to the modeling of protein-protein interaction was applied to the study of C-phycocyanin alphabeta dimers. The interacting pairs (alpha and beta subunits) share an almost complete structural homology, together with a general lack of sequence superposition; thus, they constitute a particularly relevant example for protein-protein interaction prediction. The present analysis is based on a description posited at an intermediate level between sequence and structure, that is, the hydrophobicity patterning along the chains. Based on the description of the sequence hydrophobicity patterns through a battery of nonlinear tools (recurrence quantification analysis and other sequence complexity descriptors), we were able to generate an explicit equation modeling alpha and beta monomers interaction; the model consisted of canonical correlation between the hydrophobicity autocorrelation structures of the interacting pairs. The general implications of this holistic approach to the modeling of protein-protein interactions, which considers the protein primary structures as a whole, are discussed.

Databases, Protein↗

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↗

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↗