Nanobodies are special derivatives of antibodies, which consist of single domain fragments. They have become of considerable interest as next-generation biotechnological tools for antigen recognition. They can be easily engineered due to their high stability and compact size. Nanobodies have three complementarity-determining regions, CDRs, which are enlarged to provide a similar binding surface to that of human immunoglobulins. Here, we propose a benchmark testing algorithm that uses 3D structures of already existing protein-nanobody complexes as initial structures followed by successive mutations on the CDR domains. The aim is to find optimum binding amino acids for hypervariable residues of CDRs. We use molecular dynamics simulations to compare the binding energies of the resulting complexes with that of the known complex and accept those that are improved by mutations. We use the MDM4-VH9 complex, (PDB id 2VYR), fructose-bisphosphate aldolase from Trypanosoma congolense (PDB id 5O0W) and human lysozyme (PDB id 4I0C) as benchmark complexes. By using this algorithm, better binding nanobodies can be generated in a short amount of time. We suggest that this method can complement existing immune and synthetic library-based methods, without a need for extensive experimentation or large libraries.

中文翻译：

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ModiBodies：一种在纳米抗体-抗原复合物中修饰纳米抗体以提高结合亲和力和特异性的计算方法

纳米抗体是抗体的特殊衍生物，由单域片段组成。它们作为用于抗原识别的下一代生物技术工具已引起相当大的兴趣。由于它们的高稳定性和紧凑的尺寸，它们可以很容易地设计。纳米抗体具有三个互补决定区 CDR，它们被扩大以提供与人免疫球蛋白相似的结合表面。在这里，我们提出了一种基准测试算法，该算法使用现有蛋白质-纳米抗体复合物的 3D 结构作为初始结构，然后在 CDR 域上进行连续突变。目的是为CDR的高变残基找到最佳结合氨基酸。我们使用分子动力学模拟将所得复合物的结合能与已知复合物的结合能进行比较，并接受通过突变改善的那些。我们使用 MDM4-VH9 复合物 (PDB id 2VYR)、来自刚果锥虫的果糖二磷酸醛缩酶 (PDB id 5O0W) 和人类溶菌酶 (PDB id 4I0C) 作为基准复合物。通过使用该算法，可以在短时间内生成更好的结合纳米抗体。我们建议这种方法可以补充现有的基于免疫和合成库的方法，而无需进行大量实验或大型库。可以在短时间内产生更好的结合纳米抗体。我们建议这种方法可以补充现有的基于免疫和合成库的方法，而无需进行大量实验或大型库。可以在短时间内产生更好的结合纳米抗体。我们建议这种方法可以补充现有的基于免疫和合成库的方法，而无需进行大量实验或大型库。