US-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes

Structure comparison and alignment are of fundamental importance in structural biology studies. We developed the first universal platform, US-align, to uniformly align monomer and complex structures of different macromolecules-proteins, RNAs and DNAs. The pipeline is built on a uniform TM-score objective function coupled with a heuristic alignment searching algorithm. Large-scale benchmarks demonstrated consistent advantages of US-align over state-of-the-art methods in pairwise and multiple structure alignments of different molecules. Detailed analyses showed that the main advantage of US-align lies in the extensive optimization of the unified objective function powered by efficient heuristic search iterations, which substantially improve the accuracy and speed of the structural alignment process. Meanwhile, the universal protocol fusing different molecular and structural types helps facilitate the heterogeneous oligomer structure comparison and template-based protein-protein and protein-RNA/DNA docking.