Sequence and structure alignments in post-AlphaFold era. (April 2023)

• Record Type: Journal Article
• Authors: Rajapaksa, Sandun; Konagurthu, Arun S.; Lesk, Arthur M.
• Is Part Of: Current opinion in structural biology. Volume 79(2023)
• Publication Date: 2023-04
• Subjects: Protein evolution -- Amino-acid sequence alignment -- Structure alignment -- Structure prediction; Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2023.102539
• Languages: English
• ISSNs: 0959-440X

Abstract

Abstract: Sequence alignment is fundamental for analyzing protein structure and function. For all but closely-related proteins, alignments based on structures are more accurate than alignments based purely on amino-acid sequences. However, the disparity between the large amount of sequence data and the relative paucity of experimentally-determined structures has precluded the general applicability of structure alignment. Based on the success of AlphaFold (and its likes) in producing high-quality structure predictions, we suggest that when aligning homologous proteins, lacking experimental structures, better results can be obtained by a structural alignment of predicted structures than by an alignment based only on amino-acid sequences. We present a quantitative evaluation, based on pairwise alignments of sequences and structures (both predicted and experimental) to support this hypothesis.