دورية أكاديمية
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In silico analysis of the different variable domain oriented single-chain variable fragment antibody-antigen complexes.

التفاصيل البيبلوغرافية
العنوان: In silico analysis of the different variable domain oriented single-chain variable fragment antibody-antigen complexes.
المؤلفون: Koçer İ; Department of Chemical Engineering, Hacettepe University, Ankara, Turkey.; Institute of Science, Hacettepe University, Ankara, Turkey., Çelik E; Department of Chemical Engineering, Hacettepe University, Ankara, Turkey.; Institute of Science, Division of Bioengineering, Hacettepe University, Ankara, Turkey.
المصدر: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Jun; Vol. 42 (9), pp. 4699-4709. Date of Electronic Publication: 2023 Jun 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE
أسماء مطبوعة: Publication: June 2012- : Oxon, UK : Taylor & Francis
Original Publication: Guilderland, NY : Adenine Press, [c1983-
مواضيع طبية MeSH: Single-Chain Antibodies*/chemistry , Single-Chain Antibodies*/immunology , Molecular Dynamics Simulation* , Receptor, ErbB-2*/immunology , Receptor, ErbB-2*/chemistry , Antigen-Antibody Complex*/chemistry , Antigen-Antibody Complex*/immunology , Protein Binding*, Humans ; Computer Simulation ; Interleukin-1beta/immunology ; Interleukin-1beta/chemistry ; Interleukin-1beta/metabolism ; Thermodynamics
مستخلص: Single-chain variable fragment (scFv) antibodies hold great potential as diagnostic tools and therapeutic agents, especially for tumor cells. Since these applications require their production with improved properties, the design strategy of scFvs is crucial for their active, soluble, and high yield expression with high affinity towards their antigens. The order of V L and V H domains is one of the important parameters that affect the expression and binding affinity properties of scFvs. In addition, the optimum order of V L and V H domains could change for each scFv. In the present study, we used computer simulation tools to evaluate the effect of variable domain orientation on structure, stability, interacting residues of scFvs, and binding free energies of scFv-antigen complexes. We selected anti-HER2 scFv, which is specific for human epidermal growth receptor 2 (HER2) overexpressed in breast cancer, and anti-IL-1β scFv against IL-1β which is an important inflammatory biomarker, as model scFvs. Molecular dynamics simulations of the scFv-antigen complexes for 100 ns resulted in stability and compactness for both scFv constructs. Interaction and binding free energies calculated by the Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) approach suggested that the relative binding energies of anti-HER2 scFv-V L V H and anti-HER2 scFv-V H V L constructs had similar binding affinity towards HER2, while a relatively more negative binding free energy obtained between anti-IL-1β scFv-V H V L and IL-1β pointed to a higher binding affinity. The in silico approach and the results obtained here could be applied as a guide for future experimental interaction studies for highly specific scFvs used as biotechnological tools.Communicated by Ramaswamy H. Sarma.
فهرسة مساهمة: Keywords: Binding free energy; GROMACS; MD simulation; VL/VH orientation; scFv
تواريخ الأحداث: Date Created: 20230608 Date Completed: 20240515 Latest Revision: 20240515
رمز التحديث: 20240515
DOI: 10.1080/07391102.2023.2222191
PMID: 37288797
قاعدة البيانات: MEDLINE
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