Sequence-specific and consequential interactions within or between proteins and/or RNAs can be predicted by identifying co-evolution of residues in these molecules. Different algorithms have been used to detect co-evolution, often using biological data to benchmark a methods ability to discriminate against indirect co-evolution. Such a benchmark is problematic, because not all the interactions and evolutionary constraints underlying real data can be known a priori. Instead, sequences generated in silico to simulate co-evolution would be preferable, and can be obtained using aCES, the software tool presented here. Conservation and co-evolution constraints can be specified for any residue across a number of molecules, allowing the user to capture a complex, realistic set of interactions. Resulting alignments were used to benchmark several co-evolution detection tools for their ability to separate signal from background as well as discriminating direct from indirect signals. This approach can aid in refinement of these algorithms. In addition, systematic tuning of these constraints sheds new light on how they drive co-evolution between residues. Better understanding how to detect co-evolution and the residue interactions they predict can lead to a wide range of insights important for synthetic biologists interested in engineering new, orthogonal interactions between two macromolecules.

中文翻译：

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ACES：共同进化模拟器产生共同变化的蛋白质和核酸序列

通过识别这些分子中残基的共同进化，可以预测蛋白质和/或 RNA 内部或之间的序列特异性和相应的相互作用。已使用不同的算法来检测协同进化，通常使用生物数据来衡量一种方法区分间接协同进化的能力。这样的基准是有问题的，因为并非所有基于真实数据的交互和进化约束都可以先验地知道。相反，用计算机生成的序列来模拟共同进化会更可取，并且可以使用此处介绍的软件工具 aCES 获得。可以为多个分子中的任何残基指定守恒和共同进化约束，从而允许用户捕获一组复杂、真实的相互作用。产生的比对用于对几种协同进化检测工具进行基准测试，以评估它们从背景中分离信号以及区分直接信号和间接信号的能力。这种方法可以帮助改进这些算法。此外，对这些约束的系统调整为它们如何驱动残基之间的共同进化提供了新的思路。更好地了解如何检测共同进化和它们预测的残基相互作用可以带来广泛的见解，这对于有兴趣在两个大分子之间设计新的正交相互作用的合成生物学家来说很重要。这些约束的系统调整为它们如何驱动残基之间的共同进化提供了新的思路。更好地了解如何检测共同进化和他们预测的残基相互作用可以带来广泛的见解，这对于有兴趣在两个大分子之间设计新的正交相互作用的合成生物学家很重要。这些约束的系统调整为它们如何驱动残基之间的共同进化提供了新的思路。更好地了解如何检测共同进化和他们预测的残基相互作用可以带来广泛的见解，这对于有兴趣在两个大分子之间设计新的正交相互作用的合成生物学家很重要。