C3d is a hallmark protein of the complement system, whose presence is critical to measure the progression of several immune diseases. Here, we propose to directly target C3d through small peptides mimicking the binding of its natural ligand, the complement regulator Factor H (FH). Through iterative computational analysis and binding affinity experiments, we establish a rationale for the structure-based design of FH-inspired peptides, leading to low-micromolar affinity for C3d and stable binding over microsecond-length simulations. Our FH-inspired peptides call now for further optimization toward high-affinity binding and suggest that small peptides are promising as novel C3d biomarkers and therapeutic tools.

中文翻译：

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因子C启发的补体C3d蛋白肽生物标志物设计。

C3d是补体系统的标志性蛋白质，其存在对于衡量几种免疫疾病的进展至关重要。在这里，我们建议通过模仿其天然配体（补体调节因子H（FH））结合的小肽直接靶向C3d。通过迭代计算分析和结合亲和力实验，我们建立了基于结构的FH启发肽的设计原理，从而导致对C3d的低微摩尔亲和力和微秒长模拟的稳定结合。我们受FH启发的肽现在需要进一步优化以实现高亲和力结合，并表明小肽有望成为新型C3d生物标志物和治疗工具。