Martin A C, Cheetham J C, Rees A R
Laboratory of Molecular Biophysics, University of Oxford, United Kingdom.
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9268-72. doi: 10.1073/pnas.86.23.9268.
To be of any value, a predicted model of an antibody combining site should have an accuracy approaching that of antibody structures determined by x-ray crystallography (1.6-2.7 A). A number of modeling protocols have been proposed, which fall into two main categories--those that adopt a knowledge-based approach and those that attempt to construct the hypervariable loop regions of the antibody ab initio. Here we present a combined algorithm requiring no arbitrary decisions on the part of the user, which has been successfully applied to the modeling of the individual loops in two systems: the anti-lysozyme antibody HyHel-5, the crystal structure of which is as a complex with lysozyme [Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C. & Davies, D. R. (1987) Proc. Natl. Acad. Sci. USA 84, 8075-8079], and the free antigen binding fragment (Fab) of the anti-lysozyme peptide antibody, Gloop2. This protocol may be used with a high degree of confidence to model single-loop replacements, insertions, deletions, and side-chain replacements. In addition, it may be used in conjunction with other modeling protocols as a method by which to model particular loops whose conformations are predicted poorly by these methods.
要具有任何价值，抗体结合位点的预测模型应具有接近通过X射线晶体学确定的抗体结构（1.6 - 2.7埃）的准确性。已经提出了许多建模方案，这些方案主要分为两类——采用基于知识方法的方案和试图从头构建抗体高变环区域的方案。在这里，我们提出一种无需用户进行任意决策的组合算法，该算法已成功应用于两个系统中单个环的建模：抗溶菌酶抗体HyHel - 5，其晶体结构是与溶菌酶的复合物[谢里夫，S.，西尔弗顿，E. W.，帕德兰，E. A.，科恩，G. H.，史密斯 - 吉尔，S. J.，芬泽尔，B. C. & 戴维斯，D. R.（1987年）《美国国家科学院院刊》84，8075 - 8079]，以及抗溶菌酶肽抗体Gloop2的游离抗原结合片段（Fab）。该方案可以高度自信地用于对单环替换、插入、缺失和侧链替换进行建模。此外，它可以与其他建模方案结合使用，作为一种对这些方法预测构象不佳的特定环进行建模的方法。
