Department of Chemistry, Rice University, Houston, TX, USA.
Department of Bioengineering, Rice University, Houston, TX, USA.
Nat Chem. 2021 Mar;13(3):260-269. doi: 10.1038/s41557-020-00626-6. Epub 2021 Feb 15.
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.
预测胶原蛋白三螺旋热稳定性的稳健方法对于理解胶原蛋白家族蛋白质的天然结构和稳定性以及设计模拟这些重要蛋白质的合成肽至关重要。在这项工作中，我们确定了单个氨基酸和氨基酸对之间相互作用赋予胶原蛋白三螺旋的相对稳定性。使用这种分析，我们创建了一个全面的算法 SCEPTTr，用于预测合成三螺旋的熔点。至关重要的是，我们的算法与每一种天然氨基酸兼容，既可以评估同三聚体又可以评估异三聚体，并且可以考虑所有可能的螺旋组成和登记，包括非规范交错螺旋。我们通过 431 个已发表的胶原蛋白三螺旋对我们的算法进行了测试和优化，以证明我们的预测系统的质量。最后，我们使用该算法成功地指导了具有高组装特异性的 ABC 异三聚体的设计。
