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Title: Real-time structural motif searching in proteins using an inverted index strategy

Abstract

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org ) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Univ. of California, San Diego, La Jolla, CA (United States)
  2. Univ. of California, San Diego, La Jolla, CA (United States); Rutgers, The States Univ. of New Jersey, Piscataway, NJ (United States)
Publication Date:
Research Org.:
Univ. of California, San Diego, La Jolla, CA (United States). RCSB Protein Data Bank
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Earth and Environmental Systems Science Division; USDOE
OSTI Identifier:
1736347
Alternate Identifier(s):
OSTI ID: 1734438
Grant/Contract Number:  
SC0019749
Resource Type:
Accepted Manuscript
Journal Name:
PLoS Computational Biology (Online)
Additional Journal Information:
Journal Name: PLoS Computational Biology (Online); Journal Volume: 16; Journal Issue: 12; Journal ID: ISSN 1553-7358
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Sequence motif analysis; RNA structure; Biological databases; Serine proteases; Polypeptides; Nucleic acids; Protein structure databases; Zinc

Citation Formats

Bittrich, Sebastian, Burley, Stephen K., and Rose, Alexander S.. Real-time structural motif searching in proteins using an inverted index strategy. United States: N. p., 2020. Web. https://doi.org/10.1371/journal.pcbi.1008502.
Bittrich, Sebastian, Burley, Stephen K., & Rose, Alexander S.. Real-time structural motif searching in proteins using an inverted index strategy. United States. https://doi.org/10.1371/journal.pcbi.1008502
Bittrich, Sebastian, Burley, Stephen K., and Rose, Alexander S.. Mon . "Real-time structural motif searching in proteins using an inverted index strategy". United States. https://doi.org/10.1371/journal.pcbi.1008502. https://www.osti.gov/servlets/purl/1736347.
@article{osti_1736347,
title = {Real-time structural motif searching in proteins using an inverted index strategy},
author = {Bittrich, Sebastian and Burley, Stephen K. and Rose, Alexander S.},
abstractNote = {Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org ) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.},
doi = {10.1371/journal.pcbi.1008502},
journal = {PLoS Computational Biology (Online)},
number = 12,
volume = 16,
place = {United States},
year = {2020},
month = {12}
}

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