Poster Presentation 14th Australian Peptide Conference 2022

A new tool for facilitating structural characterisation of peptides containing non-canonical amino acid (ncAA) by standard NMR methods (#210)

Sarah Kuschert 1 , Martin Stroet 2 , Alan E Mark 2 , Mehdi Mobli 1
  1. Centre for Advanced Imaging , The University of Queensland, St Lucia, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

 

Peptides containing ncAAs encompass a large pool of biologically active molecules including a number of important drugs. The significant structural and functional diversity found in these peptides has presented challenges to their modelling using standard protein and peptide NMR structure determination software, including the popular CYANA, XPLOR, and ARIA packages. In these cases, the presence of amino acids outside the genetic code requires additional input files not readily available. We have expanded the publicly available Automated Topology Builder (ATB, atb.uq.edu.au) to generate input files for standard NMR packages [1]. We have focused particularly on CYANA, a torsion angle dynamics software package, which has the most complex input requirements [2]. Using this tool vastly expands the utility of NMR structural characterisation of peptides and proteins that fall outside the 22 natural amino acids. In addition, this method will also reliably generate distance restraints required for the cross-linking of sidechains, which are often present in ncAA-containing peptides. With this streamlined approach we hope to improve the utility of NMR structural characterisation for the analysis of complex peptides, thereby improving our understanding of this large class of biologically active proteins and peptides

  1. Malde, A.K., et al., An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0. Journal of Chemical Theory and Computation, 2011. 7(12): p. 4026-4037.
  2. Guntert, P., Automated NMR structure calculation with CYANA. Methods in Molecular Biology, 2004. 278: p. 353-78.