Caravella Justin A, Wang Deping, Glaser Scott M, Lugovskoy Alexey
Biogen Idec Inc., 12 Cambridge Center, Cambridge, MA 02142, USA.
Curr Comput Aided Drug Des. 2010 Apr 6.
Monoclonal antibodies capable of recognizing antigens with high affinity and specificity represent a well established class of biological agents. Since the development of hybridoma technology in 1975, advances in recombinant DNA technologies and computational and biophysical methods have allowed us to develop a better understanding of the relationships between antibody sequence, structure, and function. These advances enable us to manipulate antibody sequences with the goal of improving upon, or creating new biological or biophysical properties. In this review we will focus on recent successes in using structure-guided computational methods to design antibodies and antibody-like molecules with optimized affinity and specificity to antigen and for enhancing protein stability.
能够以高亲和力和特异性识别抗原的单克隆抗体是一类成熟的生物制剂。自1975年杂交瘤技术发展以来,重组DNA技术以及计算和生物物理方法的进步使我们能够更好地理解抗体序列、结构和功能之间的关系。这些进展使我们能够操纵抗体序列,以改进或创造新的生物学或生物物理特性。在本综述中,我们将重点关注利用结构导向的计算方法设计对抗原具有优化亲和力和特异性并增强蛋白质稳定性的抗体和类抗体分子方面的最新成果。