A significant issue in structural biology is protein structure alignment. The first strategy is to think of proteins as hard bodies. However, because of conformational diversity or intricate evolutionary links between proteins, such as insertions, circular permutations, or repetitions, protein structure alignment can be extremely complicated. When this occurs, flexibility is advantageous for two reasons: (i) it can be used to compare two protein chains that have taken on different conformations as a result of interactions between proteins and ligands or post-translational modifications, and (ii) it can be used to identify conserved regions in proteins that may have distant evolutionary ties.
The authors suggest ICARUS, a novel method for flexible structural alignment based on the discovery of Protein Units, intermediate-sized structural descriptors that have survived evolution. On a dataset of extremely challenging structural alignments, ICARUS performs noticeably better than reference approaches.
The code is available at https://github.com/DSIMB/ICARUS.
Reference:
Gabriel Cretin et. al.(2023)ICARUS: flexible protein structural alignment based on Protein Units. Bioinformatics 39(8):btad459