VITAL NMR: Using chemical shift derived secondary structure information for a limited set of amino acids to assess homology model accuracy

Michael C. Brothers, Anna E. Nesbitt, Michael J. Hallock, Sanjeewa G. Rupasinghe, Ming Tang, Jason Harris, Jerome Baudry, Mary A. Schuler, Chad M. Rienstra

Research output: Contribution to journalArticle

Abstract

Homology modeling is a powerful tool for predicting protein structures, whose success depends on obtaining a reasonable alignment between a given structural template and the protein sequence being analyzed. In order to leverage greater predictive power for proteins with few structural templates, we have developed a method to rank homology models based upon their compliance to secondary structure derived from experimental solid-state NMR (SSNMR) data. Such data is obtainable in a rapid manner by simple SSNMR experiments (e.g., 13C-13C 2D correlation spectra). To test our homology model scoring procedure for various amino acid labeling schemes, we generated a library of 7,474 homology models for 22 protein targets culled from the TALOS?/SPARTA? training set of protein structures. Using subsets of amino acids that are plausibly assigned by SSNMR, we discovered that pairs of the residues Val, Ile, Thr, Ala and Leu (VITAL) emulate an ideal dataset where all residues are site specifically assigned. Scoring the models with a predicted VITAL site-specific dataset and calculating secondary structure with the Chemical Shift Index resulted in a Pearson correlation coefficient (-0.75) commensurate to the control (-0.77), where secondary structure was scored site specifically for all amino acids (ALL 20) using STRIDE. This method promises to accelerate structure procurement by SSNMR for proteins with unknown folds through guiding the selection of remotely homologous protein templates and assessing model quality.

Original languageEnglish (US)
Pages (from-to)41-56
Number of pages16
JournalJournal of Biomolecular NMR
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Chemical shift
Nuclear magnetic resonance
Amino Acids
Proteins
Labeling
Libraries

Keywords

  • Chemical shift analysis
  • Homology modeling
  • Protein structure prediction
  • Solid-state NMR spectroscopy
  • TALOS database

ASJC Scopus subject areas

  • Biochemistry
  • Spectroscopy

Cite this

VITAL NMR : Using chemical shift derived secondary structure information for a limited set of amino acids to assess homology model accuracy. / Brothers, Michael C.; Nesbitt, Anna E.; Hallock, Michael J.; Rupasinghe, Sanjeewa G.; Tang, Ming; Harris, Jason; Baudry, Jerome; Schuler, Mary A.; Rienstra, Chad M.

In: Journal of Biomolecular NMR, Vol. 52, No. 1, 01.01.2012, p. 41-56.

Research output: Contribution to journalArticle

Brothers, Michael C. ; Nesbitt, Anna E. ; Hallock, Michael J. ; Rupasinghe, Sanjeewa G. ; Tang, Ming ; Harris, Jason ; Baudry, Jerome ; Schuler, Mary A. ; Rienstra, Chad M. / VITAL NMR : Using chemical shift derived secondary structure information for a limited set of amino acids to assess homology model accuracy. In: Journal of Biomolecular NMR. 2012 ; Vol. 52, No. 1. pp. 41-56.
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