Kuroda Daisuke, Tsumoto Kouhei
Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.
Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Methods Mol Biol. 2018;1827:15-34. doi: 10.1007/978-1-4939-8648-4_2.
The immune systems protect our bodies from foreign molecules or antigens, where antibodies play important roles. Antibodies evolve over time upon antigen encounter by somatically mutating their genome sequences. The end result is a series of antibodies that display higher affinities and specificities to specific antigens. This process is called affinity maturation. Recent improvements in computer hardware and modeling algorithms now enable the rational design of protein structures and functions, and several works on computer-aided antibody design have been published. In this chapter, we briefly describe computational methods for antibody affinity maturation, focusing on methods for sampling antibody conformations and for scoring designed antibody variants. We also discuss lessons learned from the successful computer-aided design of antibodies.
免疫系统保护我们的身体免受外来分子或抗原的侵害,抗体在其中发挥着重要作用。抗体在遇到抗原时会随着时间推移通过体细胞突变其基因组序列而发生进化。最终结果是产生一系列对特定抗原具有更高亲和力和特异性的抗体。这个过程称为亲和力成熟。计算机硬件和建模算法的最新进展现在使得能够合理设计蛋白质结构和功能,并且已经发表了几篇关于计算机辅助抗体设计的研究成果。在本章中,我们简要描述抗体亲和力成熟的计算方法,重点关注抗体构象采样方法和对设计的抗体变体进行评分的方法。我们还讨论了从成功的抗体计算机辅助设计中吸取的经验教训。