Extended Data Fig. 7: Comparison of affinity fold improvements versus experimental scale.
From: Efficient evolution of human antibodies from general protein language models
Points indicate the results of affinity maturation beginning with an unmatured starting point (indicated by circles) or with a matured starting point (indicated by plus signs). The horizontal axis indicates the experimental scale in terms of variants tested or the experimental library size. The vertical axis indicates the fold improvement obtained by affinity maturation. Results from this study are plotted in black. While there is substantial uncertainty about the size of the mutational space explored by in-vivo somatic hypermutation (to include the unproductive B cell clones), we estimate a scale between 103 to 106 based on the number of B cells contained within a germinal center (about 103 to 104)76,77, the mutation rate of somatic hypermutation (about 1 mutation per kb per division)13, the doubling time of B cells (about 10 hours)76, and a timescale of a few weeks13. The results of natural affinity maturation of the unmatured antibodies in this study29,30,38, are plotted as blue dots (Supplementary Data 1). We also plot the results of recent studies reporting advances in antibody engineering technologies, including Mason et al.28 who achieve a 3-fold improvement in the binding of trastuzumab to human epidermal growth factor receptor 2 (HER2) using a library of ~39 K variants and Wellner et al.14 who achieve between a 2.3- and 580-fold improvement in the binding of unmatured nanobodies to SARS-CoV-2 RBD (picked out of a naïve library) using a continuously evolving yeast system involving 106 to 107 sorted cells over four or more rounds of selection.
