4 research outputs found
Joint Evolutionary Trees: A Large-Scale Method To Predict Protein Interfaces Based on Sequence Sampling
The Joint Evolutionary Trees (JET) method detects protein interfaces, the core
residues involved in the folding process, and residues susceptible to
site-directed mutagenesis and relevant to molecular recognition. The approach,
based on the Evolutionary Trace (ET) method, introduces a novel way to treat
evolutionary information. Families of homologous sequences are analyzed through
a Gibbs-like sampling of distance trees to reduce effects of erroneous multiple
alignment and impacts of weakly homologous sequences on distance tree
construction. The sampling method makes sequence analysis more sensitive to
functional and structural importance of individual residues by avoiding effects
of the overrepresentation of highly homologous sequences and improves
computational efficiency. A carefully designed clustering method is parametrized
on the target structure to detect and extend patches on protein surfaces into
predicted interaction sites. Clustering takes into account residues'
physical-chemical properties as well as conservation. Large-scale application of
JET requires the system to be adjustable for different datasets and to guarantee
predictions even if the signal is low. Flexibility was achieved by a careful
treatment of the number of retrieved sequences, the amino acid distance between
sequences, and the selective thresholds for cluster identification. An iterative
version of JET (iJET) that guarantees finding the most likely interface residues
is proposed as the appropriate tool for large-scale predictions. Tests are
carried out on the Huang database of 62 heterodimer, homodimer, and transient
complexes and on 265 interfaces belonging to signal transduction proteins,
enzymes, inhibitors, antibodies, antigens, and others. A specific set of
proteins chosen for their special functional and structural properties
illustrate JET behavior on a large variety of interactions covering proteins,
ligands, DNA, and RNA. JET is compared at a large scale to ET and to Consurf,
Rate4Site, siteFiNDER|3D, and SCORECONS on specific structures. A significant
improvement in performance and computational efficiency is shown
Methodology for Anti Gene Anti IGI I Therapy of Malignant Tumours
13The aim of this study was to establish the criteria for methodology of cellular “anti-IGF-I” therapy of malignant tumours
and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and
chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix
expression vectors. The prepared cell “vaccines” should it be in the case of glioblastomas or other tumours, have shown a change of
phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed
after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8+ and
CD8+28+ molecules and a switch from CD8+11b+ to CD8+11. All cancer patients were supervised for up to 19 months, the period
corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria
for “anti-IGF-I” strategy: characteristics sine qua non of injected “vaccines” (cloned cells IGF-I(−) and MHC-I(+)) and of PBL
cells (CD8+ increased level