Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
J Mol Biol. 2013 Feb 8;425(3):475-8. doi: 10.1016/j.jmb.2012.11.031. Epub 2012 Dec 3.
Engineered antibodies are emerging as a promising class of therapeutic biomolecules, as well as having applications in medical research. Knowledge on conserved functional and structural regions within antibody domains is imperative in order to rationally design stable and specific antibodies. Of particular interest for the design of therapeutics are antibody variable and constant domains, which are responsible for antigen binding and immune response. These antibody domains are part of the larger immunoglobulin (Ig) V-class and C-class families, respectively. We find that, although both classes belong to the Ig-fold superfamily, the sets of conserved residue positions and identities differ between these classes. We exploit these evolutionary differences to derive a metric based on sequence positional entropy that distinguishes C-class from V-class sequences utilizing only sequence information. By distinguishing different domain families using sequence information alone, we enable the application of domain-specific design strategies without the need for secondary or tertiary structural information.
工程抗体作为一类有前途的治疗性生物分子正在出现，并且在医学研究中也有应用。为了合理设计稳定和特异性的抗体，了解抗体结构域内保守的功能和结构区域至关重要。对于治疗剂的设计特别感兴趣的是抗体可变和恒定结构域，它们负责抗原结合和免疫反应。这些抗体结构域分别是较大的免疫球蛋白（Ig）V 类和 C 类家族的一部分。我们发现，尽管这两类都属于 Ig 折叠超家族，但保守残基位置和身份在这两类之间存在差异。我们利用这些进化差异，基于序列位置熵得出一种度量标准，该标准仅利用序列信息即可区分 C 类和 V 类序列。通过仅使用序列信息来区分不同的结构域家族，我们可以在不需要二级或三级结构信息的情况下应用特定于结构域的设计策略。
