MS/MS Spectra Interpretation as a Statistical–Mechanics Problem

We describe a new method for peptide sequencing based on the mapping of the interpretation of tandem mass spectra onto the analysis of the equilibrium distribution of a suitably defined physical model, whose variables describe the positions of the fragmentation sites along a discrete mass index. The model is governed by a potential energy function that, at present, we derive ad hoc from the distribution of peaks in a data set of experimental spectra. The statistical–physics perspective prompts for a consistent and unified approach to de novo and database-search methods, which is a distinctive feature of this approach over alternative ones: the characterization of the ground state of the model allows the de novo identification of the precursor peptide; the study of the thermodynamic variables as a function of the (fictitious) temperature gives insight on the quality of the prediction, while the probability profiles at nonzero temperature reveal, on one hand, which fragments are more reliably predicted. On ...