肝癌细胞特异性结合单链抗体三维结构的同源模建

用MSI公司开发的计算机辅助分子设计系统模建肝癌细胞表面抗原特异性单链抗体三维结构。先分别模建VH(variable region of the heave chain)和VL(variable region of the light chain)两个结构域,然后搭建出scFv(single chain variable fragment)片段的整体三维结构,并对模建的结构进行分子力学和动力学优化;对结构的合理性验证显示模建结构是合理的。文章可为预测该特异性单链抗体的生物活性以及研制高亲和力、高特异性的双价抗体提供结构信息。

MODELING OF scFv OF HUMAN ANTIBODY AGAINST LIVER CANCER

3D Graphic model of two single-chains Fv (scFv) , named A4 and A10, against liver cancer was constructed by computer aided molecular design software. The VH (heave variable region) and VL(light variable region) domains of scFv were modeled respectively and then the whole three-dimensional structure of scFv was constructed. Based on these, the whole three-dimensional structure was refined by the methods of molecular mechanics and dynamics. It was proved by Profile-3D program to the structure of scFv was reasonable reliable. Computer graphic modeling indicated that all places of the linker, variable region of the heave (VH) and light (VL) chains were suitable. The VH region, as well as the VL region, was involved in composing the "hydrophotic pocket". The linker was isolated from VH and VL regions. The complementary determinant regions (CDRs) of VH and VL regions surrounded the "hydrophobic pocket". This study provides a structural basis for analyzing the functions of scFv and developing bispecific antibody with high affinity and specificity.