PubMed Health⌕ Search

Biomedical subjects

C Delisi

Publications and source records attributed to C Delisi.

6 recordsLinked to original sources
PubMed1990

Determining minimum energy conformations of polypeptides by dynamic programming.

A combinatorial optimization approach is used for solving the multiple-minima problem when determining the low-energy conformations of short polypeptides. Each residue is represented by a finite number of discrete states corresponding to single residue local minima of the energy function. These precomputed values constitute a search table and define the conformational space for discrete minimization by a generalized dynamic programming algorithm that significantly limits the number of intermediate conformations to be generated during the search. Since dynamic programming involves stagewise decisions, it results in buildup-type procedures implemented in two different forms. The first procedure predicts a number of conformations by a completely discrete search and these are subsequently refined by local minimization. The second involves limited continuous local minimization within the combinatorial algorithm, generally restricted to two dihedral angles in a buildup step. Both procedures are tested on 17 short peptides previously studied by other global minimization methods but involving the same potential energy function. The discrete method is extremely fast, but proves to be successful only in 14 of the 17 test problems. The version with limited local minimization finds, however, conformations in all the 17 examples that are close to the ones previously presented in the literature or have lower energies. In addition, results are almost independent of the cutoff energy, the most important parameter governing the search. Although the limited local minimization increases the number of energy evaluations, the method still offers substantial advantages in speed.

Algorithms↗
PubMed1987

Prediction of immunodominant helper T cell antigenic sites from the primary sequence.

We have used a data base of 23 known immunodominant helper T cell antigenic sites located on 12 proteins to systematically develop an optimized algorithm for predicting T cell antigenic sites. The algorithm is based on the amphipathic helix model in which antigenic sites are postulated to be helices with one face predominantly polar and the opposite face predominantly apolar. Such amphipathic structures can form when the polarity of residues along the sequence varies with a more or less regular period. Hence they can be identified by methods (so called power spectrum procedures) that detect periodic variations in properties of a sequence. The choice of power spectrum procedure, hydrophobicity scale, and model parameters are examined. An algorithm is tested by comparing the predicted amphipathic segments with the locations of the known T cell sites, counting the number of matches, and calculating the probability of getting this number by chance alone. The optimum algorithm, which predicts the largest number of sites with the lowest chance probability, uses the Fauchere-Pliska hydrophobicity scale and a least squares fit of a sinusoid as its power spectrum procedure. By applying this algorithm, 18 of the 23 known sites are identified (75% sensitivity) with a high degree of significance (p less than 0.001). The success of the algorithm supports the hypothesis that stable amphipathic helices are fundamentally important in determining immunodominance. This approach may be of practical value in designing synthetic vaccines aimed at T cell immunity.

Algorithms↗
PubMed1978

Degradation of nucleic acid in aqueous solution by ionizing radiation. III. The correlation of radiation damage with change in melting transition--model experiments.

The melting behavior of polydeoxynucleotide double helices of known structure is analyzed in terms of the thermodynamics of helix stability, taking into account separately those contributions to the transition free energy that are proportional to the numbers of polymer molecules and those that are proportional to the numbers of base pairs formed. From the analysis of the melting transitions of helices having an alternating (d-)A.T, G.C base-pair sequence and containing either single-strand nicks or both nicks and damaged thymine bases, the effects of these structural lesions are assessed; it is concluded that, in a moderately long helix of this sequence (400 base pairs), the initial introduction of one mid-chain double-strand break or single-strand break produces respectively some 3.5 or 4 times as much depression in the transition temperature (Tm) as does the destruction of a single internal A.T base pair.

DNA, Single-Stranded↗
PubMed1977

Micrometastases formation: a probabilistic model.

A mathematical model of the process of metastases is formulated in which the hematogenous metastatic process from a solid tumor is considered to consist of a series of stages. A mathematical expression is obtained for the probability that no metastases will have been established by a characteristic time interval after tumor initiation. The murine T241 fibrosarcoma that rapidly and reproduceably produces pulmonary metastases was studied. Estimates of parameters required for the expression of probability of metastases formation were derived experimentally. The probability remains close to one for a characteristic time at which point it drops to zero. This indicates that at least in this experimental system there is a predictable critical time period beyond which micrometastases are virtually certain to have been formed.

Animals↗