The improvement of Anti-CD۲۰ Antibody Affinity with site-specific mutagenesis in CDR۳ (Tyr۱۰۱ to Arg)
- سال انتشار: 1400
- محل انتشار: کنفرانس بین المللی ژنتیک و ژنومیکس انسانی
- کد COI اختصاصی: CHGGE01_165
- زبان مقاله: انگلیسی
- تعداد مشاهده: 206
نویسندگان
Department of Biology, Faculty of science, Yazd University, Yazd, Iran
Department of Biology, Faculty of science, Yazd University, Yazd, Iran
Department of Biology, Faculty of science, Yazd University, Yazd, Iran
Department of Biology, Faculty of science, Yazd University, Yazd, Iran
چکیده
Backgrounds: CD۲۰ is a membrane glycosylated phosphoprotein that first appears in the pro-Bphase and increases in abundance as the cells mature. Based on the developmental stage of theleukemia cells, CD۲۰ is a suitable target for chemotherapy. Several anti-CD۲۰ monoclonalAntibodies are already available such as rituximab and obinutuzumab and are used for thetreatment of B-cell leukemias and lymphomas in clinical trials. One of the ways to increase theefficiency of antibodies is the site-specific mutagenesis method.Materials and Methods: In this study is used in silico site-directed mutagenesis coupled withdocking simulations of models for anti-cd۲۰ antibodies to investigate how specific amino acidsubstitutions impact ligand-protein interaction. We mutated the T (tyrosine) ۱۰۱ to R (arginine)in the CDR۳ region, the most involved region in binding to CD۲۰, using PyMol software anddocked it to the CD۲۰ using the HADDOCK program. PyMol was also used to evaluate theamino acids involved in the interaction.Results: The best complex predicted by HADDOCK was selected based on the Z-score and theenergy levels of native and mutant antibodies. The amount of van der Waals energy decreasedand the amount of electrostatic energy and the number of amino acids involved in the interactionincreased in mutant compared to the native.Conclusion: Collectively, the binding of the antibody to CD۲۰ was improved by Y۱۰۱Rmutation. So, by increasing the efficiency of antibodies, they can be used as a candidate withhigh sensitivity in the treatment of cancer.کلیدواژه ها
CD۲۰, CDR۳, cancer, monoclonal antibodyاطلاعات بیشتر در مورد COI
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