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Expanding SeqAPASS Capabilities to Protein Structural Comparisons Across Species
Citation:
Lalone, C., M. Botz, P. Schumann, W. Melendez, A. Wilkinson, AND C. Simmons. Expanding SeqAPASS Capabilities to Protein Structural Comparisons Across Species. SETAC, Dublin, IRELAND, April 30 - May 04, 2023. https://doi.org/10.23645/epacomptox.22587898
Impact/Purpose:
The US Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqapass.epa.gov/seqapass/) was developed to comparatively evaluate protein sequence and structural similarity across species as a means to extrapolate toxicity data/knowledge. SeqAPASS output provides a prediction of chemical susceptibility based on principles of evolutionary biology in understanding species relatedness at the molecular level. New to SeqAPASS Version 7 include the following: Prioritize sequences from Level 1 Primary Amino Acid Sequence Alignments and create FASTA formated sequence files Submit FASTA sequences to Iterative Threading ASSEmbly Refinement (I-TASSER) to generate protein structures in PDB formatted files along with metrics describing the quality of the structures Select protein structures generated from I-TASSER and AlphaFold to align in TM-align to produce similarity metrics that are used to describe protein conservation across species to be used to predict chemical susceptibility.
Description:
The availability of protein strucutres has expanded significantly with advances in artificial intellgence. Specificially, AlphaFold (https://alphafold.ebi.ac.uk/) and MetaAI ESM Metagenomic Atlas (https://esmatlas.com/), which house the structures for hundreds of millions of AI predicted proteins from the diversity of species. The Protein Data Bank (PDB; https://www.rcsb.org/) contains empircially derived protein structures and other approaches, such as Iterative Threading ASSEmbly Refinement (I-TASSER; (https://zhanggroup.org/I-TASSER/), provide means for additional protein structure predictions. With these advances in predicitng protein structures comes opportunity to enhance the ability to compare species at the molecular level. Such compaisons lead to understanding similarities and differences across species that can improve understanding of chemical-protein interactions and conserved biological pathways. Protein sequence comparisons for conservation across species have been used as the primary evaluation in the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) tool for predictions of chemical susceptibility and pathway conservation. However, the intent of the SeqAPASS developers is to take advantage of all exising protein information as it becomes available and tools become more amenable to automation for using these data for predictions of cross species susceptibility. Therefore, SeqAPASS version 7.0 includes new features integrated in the interface to generate and capture protein structural models from the sequences aligned in Level 1 (primary amino acid sequence alignment), compare protein structures across species for an additional line of evidnece toward protein conservation, and provide users with the protein structures for more advanced molecular docking, virtual screeening, and possibly molecular dynamic simulaiton. Moving beyond protein sequence based predictions to structure using the SeqAPASS web-based pipeline has led to enhanced understanding of the likilihood for chemcial interactions, allowing advanced users of the tool the ability to examine binding affinities. This presentation will describe the new features of SeqAPASS v7.0 and demonstrate the utility of the enhanced features.
URLs/Downloads:
DOI: Expanding SeqAPASS Capabilities to Protein Structural Comparisons Across Species
POSTER.PDF (PDF, NA pp, 2732.441 KB, about PDF)