UC San Diego researchers eliminate drug discovery bottleneck

The algorithms make use of data on the weights of the various NRP ring fragments collected at each stage using mass spectrometry. This work is an extension of an award-winning automated approach Bandeira and colleagues used to reconstruct snake venom peptides.

“Our Recomb 2008 paper represents the first demonstration of de novo sequencing of nonribosomal peptides. Without knowing the structure of the original compound, we can determine it,” explains computer science professor Pavel Pevzner, the last author on the RECOMB 2008 paper and the director of UCSD’s Center for Algorithmic and Systems Biology which is part of the UCSD Division of the California Institute for Telecommunications and Information Technology (Calit2).

In their RECOMB 2008 paper, the researchers document how they used de novo sequencing to determine the structure of two different nonribosomal peptides. In order to be able to verify their results, the researchers chose peptides that had been independently sequenced using a slow, labor intensive, costly and somewhat inconsistent nuclear magnetic resonance (NMR) approach. NMR provides information on the position of specific atoms within a molecule by using the magnetic properties of nuclei. The team is now working on more than ten additional compounds and has filed a provisional patent for the technique.

This project arose after Roger Linington from UC Santa Cruz, a co-author on the RECOMB 2008 paper, approached Dorrestein with the hope that Dorrestein’s group would be able to use mass spectrometry to obtain the molecular structure of a natural compound that is very effective against malaria. When Dorrestein found that the data being collected from a strictly mass spectrometer approach was getting extremely complicated – in large part due to the cyclic structure of the compound, he contacted Pevzner. What followed was a fruitful back and forth between the mass spectrometry team and the computer scientists that eventually led to this novel and creative solution.

"De Novo Sequencing of Nonribosomal Peptides," presented at RECOMB 2008 by Nuno Bandeira, Julio Ng, Dario Meluzzi, Pieter Dorrestein and Pavel A. Pevzner from University of California, San Diego, USA; Roger G. Linington from University of California, Santa Cruz, USA

Corresponding author: Pavel Pevzner