RosettaCM for antibodies with very long HCDR3s and low template availability.
RosettaCM for antibodies with very long HCDR3s and low template availability.
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DOI：
10.1002/prot.26166
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发表时间：
2021-11
期刊：
影响因子：
2.9
通讯作者：
Meiler J
中科院分区：
文献类型：
--
作者：
Kodali P;Schoeder CT;Schmitz S;Crowe JE , Jr;Meiler J
抗体-抗原共晶体结构对于理解抗体介导的免疫是一个有价值的资源。然而，确定抗体与其抗原形成复合体的结构是一项艰巨的任务，并不能保证成功。因此，抗体的同源建模及其与各自抗原的对接已成为推动抗体和疫苗设计的一项非常重要的技术。抗体建模过程的质量对这些努力的成功至关重要。在这里，我们比较了生物分子建模软件Rosetta中从序列预测抗体结构的不同计算协议-所有这些协议都使用多个现有的抗体结构来指导建模。具体地说，我们比较了专门为预测抗体结构而开发的协议(RosettaAbPredict)和通用同源建模协议(RosettaCM)。随着同时使用多个模板进行同源建模的最新进展，我们提出在相同抗体区域使用多个模板可能会提高建模性能。为了评估RosettaCM的多模板比较建模是否可以提高抗体的建模精度，本研究比较了三种建模算法在对来自抗体-抗原共晶体结构的人抗体进行建模时的性能。在这些基准实验中，当使用较长的HCDR3和较少的可用模板对抗体进行建模时，RosettaCM的表现优于其他方法。
Antibody-antigen co-crystal structures are a valuable resource for the fundamental understanding of antibody-mediated immunity. Determination of structures with antibodies in complex with their antigens, however, is a laborious task without guarantee of success. Therefore, homology modeling of antibodies and docking to their respective-antigens has become a very important technique to drive antibody and vaccine design. The quality of the antibody modeling process is critical for the success of these endeavors. Here, we compare different computational protocols for predicting antibody structure from sequence in the biomolecular modeling software Rosetta - all of which use multiple existing antibody structures to guide modeling. Specifically, we compare protocols developed solely to predict antibody structure (RosettaAntibody, AbPredict) with a universal homology modeling protocol (RosettaCM). Following recent advances in homology modeling with multiple templates simultaneously, we propose that the use of multiple templates over the same antibody regions may improve modeling performance. To evaluate whether multi-template comparative modeling with RosettaCM can improve the modeling accuracy of antibodies over existing methods, this study compares the performance of the three modeling algorithms when modeling human antibodies taken from antibody-antigen co-crystal structures. In these benchmarking experiments, RosettaCM outperformed other methods when modeling antibodies with long HCDR3s and few available templates.
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影响因子：
6.2
作者：
Crowe, James E., Jr.;Koff, Wayne C.
通讯作者：
Koff, Wayne C.
影响因子：
2.9
作者：
Norn, Christoffer H.;Lapidoth, Gideon;Fleishman, Sarel J.
通讯作者：
Fleishman, Sarel J.
影响因子：
3.7
作者：
Nivón LG;Moretti R;Baker D
通讯作者：
Baker D
影响因子：
64.8
作者：
Nybakken GE;Oliphant T;Johnson S;Burke S;Diamond MS;Fremont DH
通讯作者：
Fremont DH
DOI：
10.1038/nsb0996-763
发表时间：
1996-09-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Momany, C;Kovari, LC;Rossmann, MG
通讯作者：
Rossmann, MG