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C Delisi

Publications and source records attributed to C Delisi.

15 recordsLinked to original sources
PubMed1994

Predicting immunoglobulin-like hypervariable loops.

A two-stage method is developed to search the conformational space of small protein segments for low energy structures. Central features of the method are efficient procedures for generating small, eight-backbone atom, local moves in Cartesian coordinates and for introducing geometric constraints in adaptable Monte Carlo procedures. This allows natural implementation of an adaptive simulated annealing algorithm, which achieves an effective trade-off between speed and acceptance ratio. The method is applied to the calculation of various immunoglobulin loops. We also develop data base derived rules for identifying constraint condition, and show that the incorporation of an identified side-chain constraint allows a 1.2 A all-backbone atom rms deviation prediction of a 9 residue long L1 loop.

Immunoglobulin Variable Region↗
PubMed1994

Minimal requirements for peptide mediated activation of CD8+ CTL.

A physical chemical model of T cell stimulation by class I-peptide complexes was developed and used to analyse in vitro studies of gamma-interferon release as a function of the number of peptide and MHC molecules. The analysis provided reasonable estimates of well identified parameters, including equilibrium constants and the minimum number of T cell receptor-class I-peptide ternary complexes on a presenting cell required to activate T cells. The latter number was estimated as 3-5 per T cell. This is in distinct contrast to estimates in the literature of the number of peptide-MHC complexes required for activity, which is necessarily larger. The analysis also predicted that activity is potentiated by interaction between class I molecules, even if one member of the pair is not bound by antigen. The analytical approach used in this paper may be applicable to other activation systems.

3T3 Cells↗
PubMed1993

Exhaustive conformational search and simulated annealing for models of lattice peptides.

We consider simple lattice models for short peptide chains whose states can be exhaustively enumerated to find the lowest energy conformation. Using these exact results and numerical simulations, we compute the distributions for the mean time tN, required to find the global minimum energy state by simulated annealing (SA), as a function of N, the number of units in the chain. On the basis of scaling arguments, the time tN, to find the global minimum energy of longer chains, beyond the range covered by exhaustive enumeration, can be estimated. On the basis of the observed exponential increase in folding time of the standard SA algorithms, it is imperative that better algorithms be found for minimizing longer chains.

Algorithms↗
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↗
PubMed1982

A method for determining whether the descending limb of a biphasic histamine release curve reflects insufficient cross-linking.

We introduce a kinetic method for determining whether the descending limb of a biphasic histamine release dose-response curve is the result of insufficient cross-linking, and delineate conditions under which it is applicable. The method involves examining kinetic curves showing for various fixed antigen concentrations the cumulative amount of histamine release as a function of time. From the slope of the kinetic curves measured at some fixed time one determines how the rate of release depends on concentration. We show under very general conditions that if the dose-response curve for histamine release reaches a peak, and then decreases over a concentration interval in which the rate of release does not decline, then the decline in the dose-response curve cannot be due to insufficient cross-linking. Consequently, a characteristic feature of antigen-excess inhibition of histamine release due to mechanisms other than insufficient cross-linking is the crossing of a kinetic curve generated at a suboptimal antigen concentration by a kinetic curve generated at a supraoptimal antigen concentration. We show that the technique is easily executed experimentally and provide kinetic evidence-suggesting that the rabbit basophils the antigen-excess inhibition of histamine release by bis-benzylpenicilloyl-1,6-diaminohexane (BPO2) is due to insufficient cross-linking, whereas the antigen-excess inhibition observed with ovalbumin probably is due to more complete desensitization mechanisms.

Animals↗
PubMed1982

Modulation of the immune response to lipopolysaccharide.

Mice given a single optimally immunogenic dose (20 micrograms) of bacterial LPS make an antibody response that is characterized by cyclic (oscillatory) patterns. This kinetic pattern is dose as well as mouse strain dependent. LPS can induce a secondary response in BALB/c mice that is also cyclic, although it differs in amplitude as well as periodicity from a primary response. To rule out the involvement of B cell mitogenic activity of LPS in the expression of such cyclic patterns, the responses produced by both C3H/HeN and C3H/HeJ mice to a single injection of LPS were compared; the latter do not give B cell proliferative responses to LPS and also have been reported to give low LPS-specific responses in vivo. Both strains gave an oscillatory kinetic pattern. By contrast, BALB/c nu/nu mice given an optimal immunogenic dose of LPS (2 micrograms) do not present a cyclic immune response. This indicates that mature T cells are required for the generation of an oscillatory anti-LPS response.

Animals↗
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↗
PubMed1971

Prediction of RNA secondary structure.

Calculations of the free energy required to close single-strand loops by formation of a base pair in double-helical nucleic acids are reported. These results can be used to estimate the free energy of particular secondary structures for a given RNA molecule under conditions of high-salt concentration.

Models, Theoretical↗