ArticlePloS one2023
The difficulty of aligning intrinsically disordered protein sequences as assessed by conservation and phylogeny.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed.
- Sequence Conservation and Functional Significance of Charged Clusters in Mitochondria-Located Proteins of Green Plants.Journal of molecular evolution · 2026Article
- Accurate Generation of Conformational Ensembles for Intrinsically Disordered Proteins with IDPFold.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protein language model identifies disordered, conserved motifs implicated in phase separation.eLife · 2025Article
- Protein Structural Phylogenetics.Genome biology and evolution · 2025Review
- SHARK: web server for alignment-free homology assessment for intrinsically disordered and unalignable protein regions.Nucleic acids research · 2025Article
- ProtMamba: a homology-aware but alignment-free protein state space model.Bioinformatics (Oxford, England) · 2025Article
- Conformational Analyses of the AHD1-UBAN Region of TNIP1 Highlight Key Amino Acids for Interaction with Ubiquitin.Biomolecules · 2025Article
- ASR gene family: a case of tandem-drive evolution.Frontiers in molecular biosciences · 2025Article
- Sequence Analysis and Modeling of the Repetitive Region of the Long Isoform of Clarinet/CLA-1.microPublication biology · 2025Article
- Advancements in one-dimensional protein structure prediction using machine learning and deep learning.Computational and structural biotechnology journal · 2025Review
- SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Assessing the role of evolutionary information for enhancing protein language model embeddings.Scientific reports · 2024Article
- Decoding functional proteome information in model organisms using protein language models.NAR genomics and bioinformatics · 2024Article
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3 authors.
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Abstract
Intrinsically disordered proteins (IDPs) are proteins that lack a stable 3D structure but maintain a biological function. It has been frequently suggested that IDPs are difficult to align because they tend to have fewer conserved residues compared to ordered proteins, but to our knowledge this has never been directly tested. To compare the alignments of ordered proteins to IDPs, their multiple sequence alignments (MSAs) were assessed using two different methods. The first compared the similarity between MSAs produced using the same sequences but created with Clustal Omega, MAFFT, and MUSCLE. The second assessed MSAs based on how well they recapitulated the species tree. These two methods measure the "correctness" of an MSA with two different approaches; the first method measures consistency while the second measures the underlying phylogenetic signal. Proteins that contained both regions of disorder and order were analyzed along with proteins that were fully disordered and fully ordered, using nucleotide, codon and peptide sequence alignments. We observed that IDPs had less similar MSAs than ordered proteins, which is most likely linked to the lower sequence conservation in IDPs. However, comparisons of tree distances found that trees from the ordered sequence MSAs were not significantly closer to the species tree than those inferred from disordered sequence MSAs. Our results show that it is correct to say that IDPs are difficult to align on the basis of MSA consistency, but that this does not equate with alignments being of poor quality when assessed by their ability to correctly infer a species tree.
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