Date of Completion
2023
Document Type
Thesis
Degree Name
Bachelor of Science in Biochemistry
Keywords
Cotransin, Sec61, co-translational translocation, TNF-α, autoimmune diseases, molecular docking
Abstract
Cotransin is a cyclic heptadepsipeptide that inhibits the co-translational translocation process by binding to the Sec61 translocon. It reduces TNF-α expression, which is involved in inflammatory responses in autoimmune diseases. In this study, cotransin analogs were designed using SeeSAR and underwent molecular docking using the basic docking protocol of AutoDock Vina. Derivatives KCT-16, KCT-61, KCT-13, and KCT-14 gave the best binding affinities namely, -8.49 kcal/mol, -8.231 kcal/mol, -7.85 kcal/mol, and -7.85 kcal/mol which are more negative compared to cotransin’s -7.07 kcal/mol. In addition, results from SwissADME showed that the four analogs are non-orally bioavailable. Moreover, prediction of toxicity using OSIRIS and PASS Online showed that there are no toxicity risks such as mutagenicity and tumorgenicity. Molecular dynamics simulation is recommended to eliminate false positives. This may be followed by synthesis and evaluation of drug candidates using in vitro and in vivo studies.
First Advisor
Margel C. Bonifacio
APA Citation
Canlas, N. P., Kwong, T. E., & Ting, R. S. (2023). Computer-aided design of cotransin analogs as sec61 inhibitors for autoimmune disease. [Bachelor's thesis, De La Salle Medical and Health Sciences Institute]. GreenPrints. https://greenprints.dlshsi.edu.ph/bch/110