HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes.
HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes.
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DOI：
10.1038/s41467-023-42163-z
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发表时间：
2023-10-10
影响因子：
16.6
通讯作者：
Sgourakis, Nikolaos G.
中科院分区：
文献类型：
--
作者：
Gupta, Sagar;Nerli, Santrupti;Kandy, Sreeja Kutti;Mersky, Glenn L.;Sgourakis, Nikolaos G.
主要组织相容性复合体（MHC-I）的I类蛋白质在细胞表面上展示源自内源性蛋白质的表位肽用于免疫监视。与人MHC HLA结合的肽的精确建模一直受到中心肽残基的构象多样性的困扰，这对于T细胞受体的识别至关重要。在这里，我们策划的数据库（HLA 3DB）中的X射线晶体结构的分析表明，包含多种HLA同种异型的pHLA复合物呈现一组离散的肽骨架构象。利用这些骨干，我们采用回归模型训练的物理相关的能量函数，开发一个比较建模方法命名为RepPred的九聚体pHLA结构。我们的方法在结构准确性方面优于顶级pHLA建模方法高达19%，并且始终预测未包含在我们的训练集中的盲目标。从我们的工作的见解可以应用于预测抗原免疫原性，和受体交叉反应性。肽/HLA（pHLA）复合物的结构预测由于不能准确地模拟肽的中间而陷入困境。在这里，作者提出了一个策划的pHLA结构数据库（HLA 3DB），并确定了用于高保真建模的离散肽骨架构象。
The class I proteins of the major histocompatibility complex (MHC-I) display epitopic peptides derived from endogenous proteins on the cell surface for immune surveillance. Accurate modeling of peptides bound to the human MHC, HLA, has been mired by conformational diversity of the central peptide residues, which are critical for recognition by T cell receptors. Here, analysis of X-ray crystal structures within our curated database (HLA3DB) shows that pHLA complexes encompassing multiple HLA allotypes present a discrete set of peptide backbone conformations. Leveraging these backbones, we employ a regression model trained on terms of a physically relevant energy function to develop a comparative modeling approach for nonamer pHLA structures named RepPred. Our method outperforms the top pHLA modeling approach by up to 19% in structural accuracy, and consistently predicts blind targets not included in our training set. Insights from our work may be applied towards predicting antigen immunogenicity, and receptor cross-reactivity. Structure prediction of peptide/HLA (pHLA) complexes has been mired by the inability to accurately model the middle of the peptide. Here, the authors present a curated database of pHLA structures (HLA3DB) and identify discrete peptide backbone conformations that are used for high fidelity modelling.
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影响因子：
3.7
作者：
Das R
通讯作者：
Das R
影响因子：
82.9
作者：
Chandran, Smita S.;Ma, Jiaqi;Klatt, Martin G.;Dundar, Friederike;Bandlamudi, Chaitanya;Razavi, Pedram;Wen, Hannah Y.;Weigelt, Britta;Zumbo, Paul;Fu, Si Ning;Banks, Lauren B.;Yi, Fei;Vercher, Enric;Etxeberria, Inaki;Bestman, Watchain D.;Da Cruz Paula, Arnaud;Aricescu, Ilinca S.;Drilon, Alexander;Betel, Doron;Scheinberg, David A.;Baker, Brian M.;Klebanoff, Christopher A.
通讯作者：
Klebanoff, Christopher A.
影响因子：
14.9
作者：
Barker, Dominic J.;Maccari, Giuseppe;Georgiou, Xenia;Cooper, Michael A.;Flicek, Paul;Robinson, James;Marsh, Steven G. E.
通讯作者：
Marsh, Steven G. E.
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
14.9
作者：
Burley SK;Bhikadiya C;Bi C;Bittrich S;Chen L;Crichlow GV;Christie CH;Dalenberg K;Di Costanzo L;Duarte JM;Dutta S;Feng Z;Ganesan S;Goodsell DS;Ghosh S;Green RK;Guranović V;Guzenko D;Hudson BP;Lawson CL;Liang Y;Lowe R;Namkoong H;Peisach E;Persikova I;Randle C;Rose A;Rose Y;Sali A;Segura J;Sekharan M;Shao C;Tao YP;Voigt M;Westbrook JD;Young JY;Zardecki C;Zhuravleva M
通讯作者：
Zhuravleva M