| Titre : | IN SILICO STUDY OF THE KRAS PROTEIN: EVALUATION OF THE EFFECTS OF POINT MUTATION ,THEIR RELATIONSHIP TO RESPONSE AND EXPLORATION OF NON-TOXIC INHIBITOR | | Type de document : | thèse | | Auteurs : | HOSROM NADIA AHMED NASSER, Auteur | | Année de publication : | 2023 | | Langues : | Anglais (eng) | | Mots-clés : | KRAS KRAS mutation KRAS inhibitor virtual screening Docking طفرة kRAS مثبط kRAS فحص افتراضي رسو mutation kRAS inhibiteur kRAS criblage virtuel Docking | | Résumé : | MAPK families play a big part in complicated cellular processes like growth, development,
change, and death (apoptosis). The Ras/Raf/MAPK (MEK) pathway is the most critical signaling cascade among the MAPK signal transduction pathways, and it plays an essential role
in the continued existence and progression of tumor cells. The formation of malignant tumors
has been found to be most frequently related to mutations in the RAS protein family. Mutations in the KRAS protein cause cell division to happen too quickly, which helps tumors
grow. Stopping KRAS mutations would stop too many cells from dividing, which would stop
the growth of tumors. Inhibiting the KRAS mutant protein has been looked at as a possible
cancer treatment to stop KRAS from changing again.
The goal of this research is to find new possible KRAS inhibitors by using virtual screening
and docking, as well as to predict, in silico, how the stability and flexibility of mutations will
affect the way the protein works.
In our research, 36 mutations that cause cancer are studied in order to predict their effects on
the stability, flexibility, and function of the protein.
In addition, 224 different compounds that have an inhibitory impact on KRAS were chosen
from the binding database. Six compounds are used in docking. This is done after toxicity
and the Lipinski and Veber rules have been looked at. The results were compared to inhibitors used as a reference, such as 0375-0604 and sotorasib (AMG510), and according to that,
we see that the BDBM29608 inhibitor has the best affinity for most mutations.
| | Numéro (Thèse ou Mémoire) : | MM0252023 | | Président : | Mouna Ouadghiri | | Directeur : | Ilham Kandoussi | | Juge : | Rachid ElJaoudi | | Juge : | Bentayebi Kaoutar |
IN SILICO STUDY OF THE KRAS PROTEIN: EVALUATION OF THE EFFECTS OF POINT MUTATION ,THEIR RELATIONSHIP TO RESPONSE AND EXPLORATION OF NON-TOXIC INHIBITOR [thèse] / HOSROM NADIA AHMED NASSER, Auteur . - 2023. Langues : Anglais ( eng) | Mots-clés : | KRAS KRAS mutation KRAS inhibitor virtual screening Docking طفرة kRAS مثبط kRAS فحص افتراضي رسو mutation kRAS inhibiteur kRAS criblage virtuel Docking | | Résumé : | MAPK families play a big part in complicated cellular processes like growth, development,
change, and death (apoptosis). The Ras/Raf/MAPK (MEK) pathway is the most critical signaling cascade among the MAPK signal transduction pathways, and it plays an essential role
in the continued existence and progression of tumor cells. The formation of malignant tumors
has been found to be most frequently related to mutations in the RAS protein family. Mutations in the KRAS protein cause cell division to happen too quickly, which helps tumors
grow. Stopping KRAS mutations would stop too many cells from dividing, which would stop
the growth of tumors. Inhibiting the KRAS mutant protein has been looked at as a possible
cancer treatment to stop KRAS from changing again.
The goal of this research is to find new possible KRAS inhibitors by using virtual screening
and docking, as well as to predict, in silico, how the stability and flexibility of mutations will
affect the way the protein works.
In our research, 36 mutations that cause cancer are studied in order to predict their effects on
the stability, flexibility, and function of the protein.
In addition, 224 different compounds that have an inhibitory impact on KRAS were chosen
from the binding database. Six compounds are used in docking. This is done after toxicity
and the Lipinski and Veber rules have been looked at. The results were compared to inhibitors used as a reference, such as 0375-0604 and sotorasib (AMG510), and according to that,
we see that the BDBM29608 inhibitor has the best affinity for most mutations.
| | Numéro (Thèse ou Mémoire) : | MM0252023 | | Président : | Mouna Ouadghiri | | Directeur : | Ilham Kandoussi | | Juge : | Rachid ElJaoudi | | Juge : | Bentayebi Kaoutar |
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