Effects of five different interchain linkers on spatial structures, stability, and antigen-binding activities of the anti-CD25 scFv by bioinformatics studies

Introduction & Objectives: Single chain fragment variable (scFv) antibodies are composed of variable heavy (VH) and variable light (VL) domains that are joined by a polypeptide linker. Several studies have focused on the effect of different length, sequence, and flexibility of linker peptides on successful construction of single-chain Fvs (scFv). The aim of this study was to find the most suitable linker peptide among of five linker peptide (GSTSGSGKPGSGEGSTKG(L1),KESGSVSSEQLAQFRSLD(L2),EGKSSGSGSESKST (L3), (GGGGS)3 (L4), and GSAGSAAGSGEF (L5)) to construct a functional anti-CD25 single-chain fragment variable (scFv) by bioinformatics studies.Materials & Methods: Here, the 3D structures of the scFv with different linkers were predicted by Robetta server and molecular dynamics simulation was performed to compare their structures and dynamics. Then, interactions between five models of scFv and human CD25 were calculated via molecular docking.Results: Comparison of molecular dynamics simulation results presented in this study showed that the model containing (Gly4Ser)3 has more stability compared to other linkers. Additionally, based on docking results, the interaction patterns in all five models and native structure were similar and scFv-L4, scFv-L5 were better than others.

کلیدواژه ها:

Single-chain variable fragment (scFv) ، Linker peptide ، Molecular modeling