AggreProt:一个用于预测和设计蛋白质中易于聚集区域的网络服务器。

AggreProt: a web server for predicting and engineering aggregation prone regions in proteins.

机构信息

Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic.

International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.

出版信息

Nucleic Acids Res. 2024 Jul 5;52(W1):W159-W169. doi: 10.1093/nar/gkae420.

Abstract

Recombinant proteins play pivotal roles in numerous applications including industrial biocatalysts or therapeutics. Despite the recent progress in computational protein structure prediction, protein solubility and reduced aggregation propensity remain challenging attributes to design. Identification of aggregation-prone regions is essential for understanding misfolding diseases or designing efficient protein-based technologies, and as such has a great socio-economic impact. Here, we introduce AggreProt, a user-friendly webserver that automatically exploits an ensemble of deep neural networks to predict aggregation-prone regions (APRs) in protein sequences. Trained on experimentally evaluated hexapeptides, AggreProt compares to or outperforms state-of-the-art algorithms on two independent benchmark datasets. The server provides per-residue aggregation profiles along with information on solvent accessibility and transmembrane propensity within an intuitive interface with interactive sequence and structure viewers for comprehensive analysis. We demonstrate AggreProt efficacy in predicting differential aggregation behaviours in proteins on several use cases, which emphasize its potential for guiding protein engineering strategies towards decreased aggregation propensity and improved solubility. The webserver is freely available and accessible at https://loschmidt.chemi.muni.cz/aggreprot/.

摘要

重组蛋白在许多应用中发挥着关键作用,包括工业生物催化剂或治疗剂。尽管在计算蛋白质结构预测方面取得了最新进展,但蛋白质的溶解度和降低聚集倾向仍然是具有挑战性的设计属性。鉴定易聚集区域对于理解错误折叠疾病或设计高效的基于蛋白质的技术至关重要,因此具有巨大的社会经济影响。在这里,我们介绍了 AggreProt,这是一个用户友好的网络服务器,它自动利用一组深度神经网络来预测蛋白质序列中的聚集倾向区域 (APR)。在经过实验评估的六肽上进行训练后,AggreProt 在两个独立的基准数据集上的表现与最先进的算法相当或优于最先进的算法。该服务器提供了每个残基的聚集曲线,并提供了溶剂可及性和跨膜倾向的信息,具有直观的界面,带有交互式序列和结构查看器,可进行全面分析。我们在几个用例中展示了 AggreProt 在预测蛋白质的差异聚集行为方面的功效,这强调了它在指导蛋白质工程策略以降低聚集倾向和提高溶解度方面的潜力。该网络服务器是免费的,可以在 https://loschmidt.chemi.muni.cz/aggreprot/ 上访问。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a682/11223854/1d16da2d5ac6/gkae420figgra1.jpg

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