Documentation by Vikram K. Mulligan (firstname.lastname@example.org), Baker Laboratory. Last modified 4 November 2017.
The repeat stretch score term (aa_repeat) is a wholebody energy that assigns a penalty to a pose based on its sequence. Specifically, it penalizes long stretches in which the same residue type repeats over and over (e.g. poly-Q sequences). This is currently only useful for filtering a design after a packing run, but the ultimate goal is to get it working with a modified form of the packer that permits packing with non-pairwise-decomposable scoring terms that can be computed quickly.
The aa_repeat_energy scoring term can be added to any existing scoring function (e.g. ref2015.wts), and should work "out of the box" with both canonical and noncanonical amino acids. It imposes a penalty for each stretch of repeating amino acids, with the penalty value depending nonlinearly on the length of the repeating stretch. By default, 1- or 2-residue stretches incur no penalty, 3-residue stretches incur a penalty of +1, 4-residue stretches incur a penalty of +10, and 5-residue stretches or longer incur a penalty of +100. Since the term is sequence-based, it is really only useful for design -- that is, it will impose an identical penalty for a fixed-sequence pose, regardless its conformation. This also means that the term has no conformational derivatives: the minimizer ignores it completely. The term is not pairwise-decomposible, but has been made packer-compatible, so it can direct the sequence composition during a packer run.
The penalty assigned to a stretch of N repeating residues is determined based on a database file. By default, the file used is:
This is what this file looks like:
The lines starting with a pound sign (#) are ignored. The relevant line is the row of numbers, which represent the penalty for a 1-, 2-, 3-, 4-, or 5-residue stretch. Stretches longer than 5 residues are assigned the 5-residue stretch penalty. The user may provide a custom .rpt_pen file using the
# The series of numbers below indicates the penalty for having 1, 2, 3, etc. of the same residue in a row. # Zero residues (empty poses) are not penalized. More than the number of residues listed results in the # last penalty being imposed. (For example, in this file, a repeat stretch of more than five residues will # be given a penalty of 100). 0.0 0.0 1.0 10.0 100.0
-aa_repeat_energy_penalty_file <filename>flag. Custom .rpt_pen files may have as many penalty values as the user wishes (i.e. 5-residue stretches are not the limit). Stretches longer than the longest specified will be assigned the penalty given to the longest specified.
AARepeatEnergy::finalize_total_energy()function, which takes a pose as input.
AARepeatEnergy::calculate_aa_repeat_energy(), which takes a vector of const owning pointers to Residue objects as input and returns a whole-pose energy value. This function can be called by external code.
source/test/core/scoring/methods/AARepeatEnergy.cxxtest.hh. This test first scores the trp cage miniprotein, which has a three-proline repeat sequence. It then adds polyalanine repeat sequences to the end of the trp cage and repeats the scoring, confirming that the expected score value results each time.