Regep Cristian, Georges Guy, Shi Jiye, Popovic Bojana, Deane Charlotte M
Department of Statistics, University of Oxford, Oxford, OX1 3LB, United Kingdom.
Doctoral Training Centre, University of Oxford, Oxford, OX1 3QU, United Kingdom.
Proteins. 2017 Jul;85(7):1311-1318. doi: 10.1002/prot.25291. Epub 2017 Apr 6.
The H3 loop in the Complementarity Determining Region of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in silico development of antibody biotherapeutics. In this article, we show that most H3s have unique structural characteristics which may explain why they are so challenging to model. We found that over 75% of H3 loops do not have a sub-Angstrom structural neighbor in the non-antibody world. Also, in a comparison with a nonredundant set of all protein fragments over 30% of H3 loops have a unique structure, with the average for all of other loops being less than 3%. We further observed that this structural difference can be seen at the level of four residue fragments where H3 loops present numerous novel conformations, and also at the level of individual residues with Tyrosine and Glycine often found in energetically unfavorable conformations. Proteins 2017; 85:1311-1318. © 2017 Wiley Periodicals, Inc.
抗体互补决定区中的H3环在其结合各种潜在抗原空间的能力中起着关键作用。它在计算建模方面也异常困难，这给抗体生物治疗药物的计算机辅助开发带来了重大障碍。在本文中，我们表明大多数H3环具有独特的结构特征，这可能解释了为什么它们在建模时如此具有挑战性。我们发现，超过75%的H3环在非抗体领域中没有亚埃级别的结构邻居。此外，与所有蛋白质片段的非冗余集相比，超过30%的H3环具有独特的结构，而所有其他环的平均值不到3%。我们进一步观察到，这种结构差异在四个残基片段的水平上就可以看到，其中H3环呈现出许多新颖的构象，在单个残基水平上也可以看到，酪氨酸和甘氨酸经常处于能量不利的构象中。《蛋白质》2017年；85:1311 - 1318。©2017威利期刊公司。
