collision-induced dissociation (CID), ETD is advantageous for the fragmentation of longer peptides or even entire proteins. This makes the technique important for top-down proteomics. Much like ECD, ETD is effective for peptides with modifications such as phosphorylation. Electron-transfer and higher-energy collision dissociation (EThcD) is a combination ETD and HCD where the peptide precursor is initially subjected to an ion/ion reaction with fluoranthene anions in a linear ion trap, which generates c- and z-ions. In the second step HCD all-ion fragmentation is applied to all ETD derived ions to generate b- and y- ions prior to final analysis in the orbitrap analyzer. This method employs dual fragmentation to generate ion- and thus data-rich MS/MS spectra for peptide sequencing and PTM localization. Negative electron-transfer dissociation Fragmentation can also occur with a deprotonated species, in which an electron is transferred from the species to an cationic reagent in a negative electron transfer dissociation (NETD): Following this transfer event, the electron-deficient anion undergoes internal rearrangement and fragments. NETD is the ion/ion analogue of electron-detachment dissociation (EDD). NETD is compatible with fragmenting peptide and proteins along the backbone at the Cα-C bond. The resulting fragments are usually a•- and x-type product ions. Electron-detachment dissociation Electron-detachment dissociation (EDD) is a method for fragmenting anionic species in mass spectrometry. It serves as a negative counter mode to electron capture dissociation. Negatively charged ions are activated by irradiation with electrons of moderate kinetic energy. The result is ejection of electrons from the parent ionic molecule, which causes dissociation via recombination. Charge-transfer dissociation Reaction between positively charged peptides and cationic reagents, also known as charge transfer dissociation (CTD), has recently been demonstrated as an alternative high-energy fragmentation pathway for low-charge state (1+ or 2+) peptides. The proposed mechanism of CTD using helium cations as the reagent is: Initial reports are that CTD causes backbone Cα-C bond cleavage of peptides and provides a•- and x-type product ions. Photodissociation The energy required for dissociation can be added by photon absorption, resulting in ion photodissociation and represented by {AB+} + \mathit{h\nu} -> {A} + B+ where represents the photon absorbed by the ion. Ultraviolet lasers can be used, but can lead to excessive fragmentation of biomolecules. Infrared multiphoton dissociation Infrared photons will heat the ions and cause dissociation if enough of them are absorbed. This process is called infrared multiphoton dissociation (IRMPD) and is often accomplished with a carbon dioxide laser and