Université Paris Cité and Université des Antilles and Université de la Réunion, INSERM, BIGR, F-75015 Paris, France.
Laboratoire d'Excellence GR-Ex, 75015 Paris, France.
Bioinformatics. 2023 Aug 1;39(8). doi: 10.1093/bioinformatics/btad459.
Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational variability, or complex evolutionary relationships between proteins such as insertions, circular permutations or repetitions. In such cases, introducing flexibility becomes useful for two reasons: (i) it can help compare two protein chains which adopted two different conformational states, such as due to proteins/ligands interaction or post-translational modifications, and (ii) it aids in the identification of conserved regions in proteins that may have distant evolutionary relationships.
We propose ICARUS, a new approach for flexible structural alignment based on identification of Protein Units, evolutionarily preserved structural descriptors of intermediate size, between secondary structures and domains. ICARUS significantly outperforms reference methods on a dataset of very difficult structural alignments.
Code is freely available online at https://github.com/DSIMB/ICARUS.
蛋白质结构的比对是结构生物学中的一个主要问题。通常使用的第一种方法是将蛋白质视为刚体。然而，由于构象变异性，或者蛋白质之间复杂的进化关系，如插入、环状排列或重复，蛋白质结构的比对可能非常复杂。在这种情况下，引入灵活性有两个原因：（i）它可以帮助比较两个采用不同构象状态的蛋白质链，例如由于蛋白质/配体相互作用或翻译后修饰，以及（ii）它有助于识别蛋白质中可能具有遥远进化关系的保守区域。
我们提出了 ICARUS，这是一种基于识别蛋白质单元的新的灵活结构比对方法，蛋白质单元是介于二级结构和结构域之间的中间大小的进化保守结构描述符。ICARUS 在非常困难的结构比对数据集上的表现明显优于参考方法。
代码可在 https://github.com/DSIMB/ICARUS 上免费获得。
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