Multistage Sequencing of Cyclic Peptides

Download   Documentation
Contact: Hosein Mohimani [hmohiman (at) ucsd.edu]

Summary

Some of the most effective antibiotics (e.g. Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of MS-based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. Our multistage cyclic peptide sequencing tool has shown its advantages over single-stage sequencing. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. The method is available online at cyclo.ucsd.edu.

Documentation

• Linux Installation
  
  run 'cmake .' and then run 'make'
  Windows users should try our webserver at cyclo.ucsd.edu.
  
  
• Run
  
  multistage_html : multistage denovo sequencing of linear/cyclic peptides
  
  The only required parameters of multistage sequencing are address of mgf/mzxml file, and the peptide length. the parameters are described below:
  

  Required arguments:
  -------------------
  <path to input mzxml/mgf file>
  length                                      peptide length
  
  Optional multistage_html arguments: 
  ----------------------------- 
  -out <path to output html file>              (default : out.html)
  -linear                                      do linear sequencing
  -num_top X       number of top search hits returned (default: 10)
  -num_peaks X    number of top peaks kept in spectra (default: 20)
  -parent_mass X                                Parent Mass (in Da)
  -standard                                use standard amino acids
  -tag X                                consider a tag of mass X Da
  -num_rand                               number of random peptides
  -correct_seq A1 ... An                   correct peptide sequence