PubMed Health⌕ Search

Biomedical subjects

T Castrignanò

Publications and source records attributed to T Castrignanò.

6 recordsLinked to original sources
PubMed2001

Structure and hydration of the DNA-human topoisomerase I covalent complex.

The structure and hydration of reconstituted human topoisomerase I comprising the core and the carboxyl-terminal domains in covalent complex with 22-basepair DNA duplex has been investigated by molecular dynamics simulation. The structure and the intermolecular interactions were found to be well maintained over the simulation. The complex displays a high degree of flexibility of the contact area, confirmed by the presence of numerous water-mediated protein-DNA hydrogen bonds comparable in quantity and distribution to the direct ones. The interaction between the enzyme and the solvent also provides the key for interpreting the experimental reduction of activity or affinity observed upon single residue mutation. Finally, four long lasting water molecules are observed in the proximity of the active site, one of which in the appropriate position to accept a proton from the active Tyr723.

Amino Acid Substitution↗
PubMed2000

Structure and hydration of BamHI DNA recognition site: a molecular dynamics investigation.

The results of a 3-ns molecular dynamics simulation of the dodecamer duplex d(TATGGATCCATA)(2) recognized by the BamHI endonuclease are presented here. The DNA has been simulated as a flexible molecule using an AMBER force field and the Ewald summation method, which eliminates the undesired effects of truncation and permits evaluation of the full effects of electrostatic forces. The starting B conformation evolves toward a configuration quite close to that observed through x-ray diffraction in its complex with BamHI. This configuration is fairly stable and the Watson-Crick hydrogen bonds are well maintained over the simulation trajectory. Hydration analysis indicates a preferential hydration for the phosphate rather than for the ester oxygens. Hydration shells in both the major and minor groove were observed. In both grooves the C-G pairs were found to be more hydrated than A-T pairs. The "spine of hydration" in the minor groove was clear. Water residence times are longer in the minor groove than in the major groove, although relatively short in both cases. No special long values are observed for sites where water molecules were observed by x-ray diffraction, indicating that water molecules having a high probability of being located in a specific site are also fast-exchanging.

Base Pairing↗
PubMed1999

A novel parameter to estimate the minimum number of bound ligands needed to activate an ion channel.

We consider the Hill coefficient obtained from concentration-response curves and we stress the differences between the use of binding and the use of current for the response. We first show that in order to estimate the cooperativity of binding sites one must use the coefficient obtained from the binding curves and not that obtained from the current curves. For what concerns the estimation of the minimum number of bound ligands needed to activate the channel, while the coefficient obtained from the binding is simply not applicable, we show that the coefficient obtained from the current is not appropriate. We finally introduce a novel parameter that predicts the number of ligand molecules required to open the channel from current measurements at very low ligand concentration. The above considerations are exemplified by a few theoretical models.

Animals↗
PubMed1998

Are only repeated triplets guilty?

It is well known that in some places of the human genome one finds a variable number of tandem repeats of trinucleotides; it is now commonly acknowledged that in many cases an excessive expansion of such a number is the cause of nervous system diseases. Moreover there exist cases of genetic disorders linked with loci where a variable number of tandem repeats of sequences longer than three bases has been found. The abnormal number of these repeats in few cases has been associated with the onset of the disease. Considering the above facts, we have performed an extensive study of published sequences of genes connected with various diseases. We have examined, inside or near those genes, all possible tandem repeats. The analysis has led to the detection of a large number of repeats of both triplets and longer sequences, many of which, as far as we know, had not been pointed out before. The results of our analysis lead us to put forward the hypothesis that in more cases than those till now established, a variable number of tandem repeats of generic sequences, not only of triplets, could be associated with disease onset. Finally we suggest to allocate experimental researches for all the possible tandem repeats and their possible correlation with the neurodegenerative disorders and with other kinds of syndromes.

Base Sequence↗
PubMed1997

A study of oligonucleotide occurrence distributions in DNA coding segments.

In this paper we present a general strategy designed to study the occurrence frequency distributions of oligonucleotides in DNA coding segments and to deal with the problem of detecting possible patterns of genomic compositional inhomogeneities and disuniformities. Identifying specific tendencies or peculiar deviations in the distributions of the effective occurrence frequencies of oligonucleotides, with respect to what can be a priori expected, is of the greatest importance in biology. Differences between expected and actual distributions may in fact suggest or confirm the existence of specific biological mechanisms related to them. Similarly, a marked deviation in the occurrence frequency of an oligonucleotide may suggest that it belongs to the class of so-called "DNA signal (target) sequences". The approach we have elaborated is innovative in various aspects. Firstly, the analysis of the genomic data is carried out in the light of the observation that the distribution of the four nucleotides along the coding regions of the genoma is biased by the existence of a well-defined "reading frame". Secondly, the "experimental" numbers found by counting the occurrences of the various oligonucleotide sequences are appropriately corrected for the many kinds of mistakes and redundancies present in the available genetic Data Bases. A methodologically significant further improvement of our approach over the existing searching strategies is represented by the fact that, in order to decide whether or not the (corrected) "experimental" value of the occurrence frequency of a given oligonucleotide is within statistical expectations, a measure of the strength of the selective pressure, having acted on it in the course of the evolution, is assigned to the sequence, in a way that takes into account both the value of the "experimental" occurrence frequency of the sequence and the magnitude of the probability that this number might be the result of statistical fluctuations. If the strength of the selective pressure evaluated in this fashion turns out to be sufficiently large, the corresponding sequence will be considered to have an occurrence frequency beyond expectations and, hence, to be statistically and biologically interesting.

Algorithms↗