Constrained de novo sequencing of peptides with applications to conotoxins

Cone snail toxins are small (10 -- 40 aa), heavily modified, cysteine-rich proteins. They are of special interest as drug leads and as probes for studying ion channels. With advances such as ETD fragmentation and high-accuracy MS/MS, it's just now becoming feasible to sequence these molecules by mass spectrometry. I'll talk about a bioinformatics approach suitable for the problem: constrained de novo sequencing, which generates and scores candidate sequences matching user-defined constraints. The constraints can vary from simple ("must contain four cysteines") to complex (a regular expression or hidden Markov model).

Citation

Bhatia, S. P.; Kil, Y. J.; Ueberheide, B.; Chait, B.; Tayo, L.; Cruz, L. J.; Lu, N.; Yates, J. R.; Bern, M. Constrained de novo sequencing of peptides with applications to conotoxins. 15th Annual International Research in Computational Molecular Biology (RECOMB); 2011 March 28-31; Vancouver, B.C., 2011. Berlin: Springer; 2011; LNCS 6577: 16-30.