CycloBranch
Cyclic Peptides

Cyclic Peptide Detail Window

The window is opened by a double-click on a row in the output report if a cyclic peptide was identified. The Enter key can also be used if the row is selected.

cyclicdetail.png
De novo sequencing of beauverolide I.

See also Linear Peptide Detail Window. The differences for cyclic peptides are following:

  • The text window on the right at the bottom contains a list of all linearized sequences derived from all possible ring break up points of a cyclic sequence.
  • A name of a fragment ion is prefixed with an identifier of a linearized peptide sequence from which the fragment ion was generated (e.g., 3-4_A1 means that the fragment ion a1 was generated from the linearized sequence 3-4).

Toolbar for Cyclic Peptides

See also Toolbar for Linear Peptides. The differences for cyclic peptides are following:

Hide Scrambled Peaks (CTRL + S)

The function is available if a cyclic peptide was searched and if the checkbox Enable Scrambling was checked. The experimental peaks which were assigned to scrambled theoretical peaks of a cyclic peptide are black if the button is checked. If the button is unchecked, the peaks are red. The scrambled peaks in the peaks table are also hidden if the button is checked.

Ring break up point

A dropdown menu where you can choose which peaks are red in the spectrum on the left and which fragment ions are shown in the visualization of a cyclic peptide on the right. You can choose that only theoretical peaks from one linearized sequence (e.g., 3-4) are red if they are matched with experimental peaks. In this case, the graphical visualization on the right shows only matched fragment ions from the linearized sequence 3-4 and the break up point 3-4 is red. The default value "all" means that all matched theoretical peaks on the left are red and that all matched fragment ions are shown on the right.


Cyclic Sequence Detection

A path in the de novo graph corresponding to a b-ion series of a cyclic peptide is detected as shown in the following scheme. An edge corresponds to a residue mass of a building block or to a sum of residue masses of a combination of building blocks. If an edge corresponds to multiple building blocks, peptide sequence candidates with all permutations of building blocks are generated from a path in a de novo graph. For example, when the edge corresponds to a combination of blocks leucine, proline and valine, the order of blocks can be LPV, LVP, PVL, PLV, VLP, and VPL; and thus 6 peptide sequence candidates are generated.

cyclic-denovo.png
Detection of a path corresponding to a cyclic peptide in a de novo graph.

Nomenclature of Cyclic Series

The names of linearized peptide sequences are derived as shown in the following figure on a showcase example of roseotoxin A. Since the peptide is composed from six building blocks, twelve series of b-ions are generated. The numbers in superscripts of the names of b-ions indicate ring opening sites (e.g., 1-6b2 means the ion b2 arise after ring opening between leucic acid and betaalanine). The first number in the superscript corresponds to the N-terminal building block (leucic acid) and the second number to the C-terminal block (betaalanine). In case of reverted linearized sequences, the first number denotes a C-terminal block and the second number an N-terminal block.

  • The ion i-jb corresponding to a linearized sequence composed from k building blocks has

    • i > j when i ≠ 1 and j ≠ k;
    • i < j when i = 1 and j = k.

  • The ion i-jb corresponding to a reverted linearized sequence composed from k building blocks has

    • i < j when i ≠ k and j ≠ 1;
    • i > j when i = k and j = 1.

Note that each fragment ion occurs twice in the scheme (e.g., the fragment ion 1-6b2 is identical with 2-3b2).

cyclicfragmentation-v2-light.png
Principle of numbering of fragment ions series of roseotoxin A (C5 = leucic acid; mP = 3-methylproline; I = isoleucine; mV = methylvaline; mA = methylalanine; bA = betaalanine).

Number of Matched Bricks

The number of matched bricks is a scoring function for cyclic peptides.

A building block is matched in three cases:

  • when two consecutive b-ions are detected in a series;
  • when the fragment ion b1 is detected;
  • when the fragment ion bn-1 is detected where n is the number of building blocks of a peptide.

The score is calculated as a sum of all matched building blocks.