Predicting the stability of homotrimeric and heterotrimeric collagen helices
Predicting the stability of homotrimeric and heterotrimeric collagen helices
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DOI：
10.1038/s41557-020-00626-6
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发表时间：
2021-02-15
期刊：
影响因子：
21.8
通讯作者：
Hartgerink，Jeffrey D.
中科院分区：
文献类型：
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作者：
Walker，Douglas R.;Hulgan，Sarah A. H.;Hartgerink，Jeffrey D.
预测胶原蛋白三螺旋热稳定性的稳健方法对于了解胶原蛋白家族的天然结构和稳定性以及设计模仿这些必需蛋白的合成肽至关重要。在这项工作中，我们确定了单个氨基酸和氨基酸对之间的相互作用赋予胶原三螺旋的相对稳定性。利用此分析，我们创建了一个综合算法 SCEPTTr，用于预测合成三螺旋的熔化温度。重要的是，我们的算法与每种天然氨基酸兼容，可以评估同源三聚体和异源三聚体，并考虑所有可能的螺旋组成和寄存器，包括非规范交错螺旋。我们针对 431 个已发表的胶原蛋白三螺旋测试并优化我们的算法，以证明我们预测系统的质量。最后，我们使用该算法成功指导了具有高组装特异性的ABC异三聚体的设计。
Robust methods for predicting thermal stabilities of collagen triple helices are critical for understanding natural structure and stability in the collagen family of proteins and also for designing synthetic peptides mimicking these essential proteins. In this work, we determine the relative stability imparted on the collagen triple helix by single amino acids and interactions between amino acid pairs. Using this analysis, we create a comprehensive algorithm, SCEPTTr, for predicting melting temperatures of synthetic triple helices. Critically, our algorithm is compatible with every natural amino acid, can evaluate both homotrimers and heterotrimers, and accounts for all possible helix compositions and registers, including non-canonically staggered helices. We test and optimize our algorithm against 431 published collagen triple helices to demonstrate the quality of our predictive system. Finally, we use this algorithm to successfully guide the design of an ABC heterotrimer possessing high assembly specificity.