Biochemical filtering of a protein-protein docking simulation identifies the structure of a complex between a recombinant antibody fragment and α-bungarotoxin
Biochemical filtering of a protein-protein docking simulation identifies the structure of a complex between a recombinant antibody fragment and α-bungarotoxin
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DOI：
10.1042/bj20021369
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发表时间：
2003-04-15
影响因子：
4.1
通讯作者：
Neri, P
中科院分区：
文献类型：
--
作者：
Bracci, L;Pini, A;Neri, P
利用对接模拟程序实现了a-bungarotoxin与模仿乙酰胆碱受体的重组抗体片段复合物的结构表征。为了将计算机模拟推向具有生物学意义的有限解决方案，采用了一种过滤器，结合抗原-抗体相互作用的一般考虑因素，所选抗体片段的特异性和a-bungarotoxin表位定位的结果。该配合物有两种相似的结构，它们都是通过抗体片段的酪基残基的阳离子- π和疏水相互作用来稳定的。位点导向诱变研究，去除后一个芳香残基，使抗体片段和神经毒素之间的相互作用过程完全失活，支持计算出的复合物结构的有效性。
The structural characterization of a complex of a-bungarotoxin with a recombinant antibody fragment that mimics the acetylcholine receptor was achieved using docking simulation procedures. To drive the computer simulation towards a limited set of solutions with biological significance, a filter, incorporating general considerations of antigen-antibody interactions, specificity of the selected antibody fragment and results from a-bungarotoxin epitope mapping, was adopted. Two similar structures were obtained for the complex, both of them stabilized by cation-pi and hydrophobic interactions due to tyrosilyl residues of the antibody fragment. Site-directed mutagenesis studies, removing each of the latter aromatic residues and causing full inactivation of the interaction process between the antibody fragment and the neurotoxin, support the validity of the calculated structure of the complex.