Di Rienzo Lorenzo, Milanetti Edoardo, Ruocco Giancarlo, Lepore Rosalba
Center for Life Nano and Neuro-Science, Istituto Italiano di Tecnologia, Rome, Italy.
Department of Physics, Sapienza University, Rome, Italy.
Front Mol Biosci. 2021 Sep 30;8:749784. doi: 10.3389/fmolb.2021.749784. eCollection 2021.
Antibodies have the remarkable ability to recognise their cognate antigens with extraordinary affinity and specificity. Discerning the rules that define antibody-antigen recognition is a fundamental step in the rational design and engineering of functional antibodies with desired properties. In this study we apply the 3D Zernike formalism to the analysis of the surface properties of the antibody complementary determining regions (CDRs). Our results show that shape and electrostatic 3DZD descriptors of the surface of the CDRs are predictive of antigen specificity, with classification accuracy of 81% and area under the receiver operating characteristic curve (AUC) of 0.85. Additionally, while in terms of surface size, solvent accessibility and amino acid composition, antibody epitopes are typically not distinguishable from non-epitope, solvent-exposed regions of the antigen, the 3DZD descriptors detect significantly higher surface complementarity to the paratope, and are able to predict correct paratope-epitope interaction with an AUC = 0.75.
抗体具有以非凡的亲和力和特异性识别其同源抗原的卓越能力。识别定义抗体 - 抗原识别的规则是合理设计和工程化具有所需特性的功能性抗体的基本步骤。在本研究中，我们将三维泽尼克形式体系应用于抗体互补决定区（CDR）表面性质的分析。我们的结果表明，CDR表面的形状和静电三维泽尼克描述符可预测抗原特异性，分类准确率为81%，受试者操作特征曲线（AUC）下的面积为0.85。此外，就表面大小、溶剂可及性和氨基酸组成而言，抗体表位通常与抗原的非表位、溶剂暴露区域无法区分，但三维泽尼克描述符检测到与抗原结合部位的表面互补性显著更高，并且能够以AUC = 0.75预测正确的抗原结合部位 - 表位相互作用。
