| Titre : |
Calculs et modélisations des intéractions peptide déformylase-substances antibacteriennes à l'aide de techniques de " Docking" (arrimage) moléculaire |
| Type de document : |
texte imprimé |
| Auteurs : |
Abdelouahab Chikhi, Auteur ; Univ. de Constantine, Éditeur scientifique ; Mustapha Bencharif, Directeur de thèse |
| Année de publication : |
2007 |
| Importance : |
123 f. |
| Note générale : |
01 Disponible à la salle de recherche 02 Disponibles au magazin de la B.U.C. 01 CD |
| Langues : |
Français (fre) |
| Catégories : |
Français - Anglais
Biologie
|
| Tags : |
Modélisations Peptide déformylase Substances antibacteriennes Intéractions Docking Flex Surflex Modelling peptide deformylase antibiotic substances interactions docking FlexX |
| Index. décimale : |
570 Sciences de la vie. Biologie |
| Résumé : |
The computer tool is currently requisite in research in biology to treat the stream of data
produced and to optimize its progress. The molecular stowage or '' docking '' is, indeed,
one of the methods commonly used in pharmacochimistry to discover and to finalize of
new medicines by screening of thousands of compounds for a protein target. The two
programs of molecular stowage, Surflex and FlexX, have been developed to help towards
the clarification of molecules with therapeutic activity. They proved to be effective enough
to reproduce the experimental tests because 88,4 % of the values of RMSD are lower
than 2 Å for the first one and 80,6 % for the second. They were used to study the inhibition
of the 1bsj, a peptide deformylase belonging to Escherichia coli, by diverse molecules of
ligands to discover the best inhibitors of the enzyme; this last one being found at most of
the pathogenic microorganisms. The results are comparable, generally, for both programs.
The first study highlighted the actinonin as the better inhibitor of the enzyme. Mono and bi
substitutions realized on the actinonin showed that it is possible to increase, in a
significant way, the affinity of the actinonin and its energy of interaction with the enzyme
by a well-judged choice of fragments to replace. Indeed, the replacement of the ethyl in
position 9, positioned at P1' region, by an amide and the pentyl, located at P3' region, by a
phenyl in the actinonin increase the affinity of more than 2 units (6.97 - 9.33) and the
energy of interaction of 10 units (-31.880 to -41.141 Kj / mole). The second study allowed
to identify the isoxazole-3-hydroxamic acid and its by-products as of new no peptidic
inhibitors of the 1bsj. Finally, the indole and its by-products, a new class of inhibitors
acting specifically on the bacterial PDF, presented satisfactory values of affinities with the
1Lry and the 1Lqy. |
| Diplôme : |
Doctorat |
| En ligne : |
../theses/biologie/CHI4998.pdf |
| Permalink : |
index.php?lvl=notice_display&id=1746 |
Calculs et modélisations des intéractions peptide déformylase-substances antibacteriennes à l'aide de techniques de " Docking" (arrimage) moléculaire [texte imprimé] / Abdelouahab Chikhi, Auteur ; Univ. de Constantine, Éditeur scientifique ; Mustapha Bencharif, Directeur de thèse . - 2007 . - 123 f. 01 Disponible à la salle de recherche 02 Disponibles au magazin de la B.U.C. 01 CD Langues : Français ( fre)
| Catégories : |
Français - Anglais
Biologie
|
| Tags : |
Modélisations Peptide déformylase Substances antibacteriennes Intéractions Docking Flex Surflex Modelling peptide deformylase antibiotic substances interactions docking FlexX |
| Index. décimale : |
570 Sciences de la vie. Biologie |
| Résumé : |
The computer tool is currently requisite in research in biology to treat the stream of data
produced and to optimize its progress. The molecular stowage or '' docking '' is, indeed,
one of the methods commonly used in pharmacochimistry to discover and to finalize of
new medicines by screening of thousands of compounds for a protein target. The two
programs of molecular stowage, Surflex and FlexX, have been developed to help towards
the clarification of molecules with therapeutic activity. They proved to be effective enough
to reproduce the experimental tests because 88,4 % of the values of RMSD are lower
than 2 Å for the first one and 80,6 % for the second. They were used to study the inhibition
of the 1bsj, a peptide deformylase belonging to Escherichia coli, by diverse molecules of
ligands to discover the best inhibitors of the enzyme; this last one being found at most of
the pathogenic microorganisms. The results are comparable, generally, for both programs.
The first study highlighted the actinonin as the better inhibitor of the enzyme. Mono and bi
substitutions realized on the actinonin showed that it is possible to increase, in a
significant way, the affinity of the actinonin and its energy of interaction with the enzyme
by a well-judged choice of fragments to replace. Indeed, the replacement of the ethyl in
position 9, positioned at P1' region, by an amide and the pentyl, located at P3' region, by a
phenyl in the actinonin increase the affinity of more than 2 units (6.97 - 9.33) and the
energy of interaction of 10 units (-31.880 to -41.141 Kj / mole). The second study allowed
to identify the isoxazole-3-hydroxamic acid and its by-products as of new no peptidic
inhibitors of the 1bsj. Finally, the indole and its by-products, a new class of inhibitors
acting specifically on the bacterial PDF, presented satisfactory values of affinities with the
1Lry and the 1Lqy. |
| Diplôme : |
Doctorat |
| En ligne : |
../theses/biologie/CHI4998.pdf |
| Permalink : |
index.php?lvl=notice_display&id=1746 |
|
Calculs et modélisations des intéractions peptide déformylase-substances antibacteriennes à l'aide de techniques de " Docking" (arrimage) moléculaire
