Quick start

The main goal of pmlbeta is to provide tools for building molecular models of β-peptides (or even mixed α/β-peptides). The idea is mostly taken from the fab command of PyMOL, which can create peptides in a desired secondary structure. The construction of β-peptides can be done by two means: either using the command-line or a graphical user interface.

Command line

The command betafab2 can be used for creating α/β-peptides in extended conformation:

betafab2 hp6, (2R3S)B23h(2A3A), (2R3S)B23h(2A3V), (S)B2hV, (S)B3hK, (2R3S)B23h(2A3A), (2R3S)B23h(2A3L)

betafab2 valxval, (S)B3hV, (S)B3hA, (S)B3hL, (2S3S)B23h(2A3A), (S)B3hV, (S)B3hA, (S)B3hL

betafab valval, (S)AV, (S)AA, (S)AL, (S)AV, (S)AA, (S)AL

betafab mixed, (S)AV, (S)B3hV, (R)B2hA, (S)AQ, (2R3S)B23h(2C3W)

The first argument is always the PyMOL object name, followed by the residue abbreviations following the notation in Simplified nomenclature

Folding a peptide into the desired secondary structure is possible by supplying the desired secondary structures for the amino-acids in betafab2:

betafab2 valxval, (S)B3hV{H14M}, (S)B3hA[-140.3 66.5 136.8], (S)B3hL{H14M}

Another option is to fold an already built peptide using the fold_bp command:

fold_bp H14M, valxval   # folds all residues the "valxval" model to the H14M helix

fold_bp (-140.3 66.5 136.8), valxval    # the same as above, just the torsion angles are explicitly given

Instead of folding the entire peptide to the same secondary structure, this can be done residue-by-residue:

betafab2 test, (S)B3hA, (S)B3hA, (S)B3hA, (S)B3hA, (S)B3hV, (S)B3hA, (S)B3hA

fold_bp [ H14M H14M H14M H14M H14M H14M H14M], test

fold_bp [ H14M (-140.3 66.5 136.8) H14M H14M H14M (-140.3 66.5 136.8) H14M], test # the same as above

Note that not every peptide sequence supports every secondary structure. For example, you will find steric clashes if you try to fold an (R)-homochiral β3-peptide into the H14M helix:

betafab2 invalid, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL

fold_bp H14M, invalid

In other cases when the sequence and the desired fold are compatible, you can still get steric clashes because the folding procedure does not touch the side-chains. Luckily these can easily be removed by the sculpting facility of PyMOL. For example, when the above peptide is produced in the default, extended conformation, there is a steric clash between the leucine side-chains and the amide oxygen. To resolve them, first fix the backbone atoms and initialize sculpting.

betafab2 clash, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL

# select the backbone -> makes a new selection (bbone)
select_bbb bbone, invalid

# fix the backbone atoms
flag fix, (bbone), set

# Initialize sculpting
sculpt_activate invalid

# Do some iterations
sculpt_iterate invalid, cycles=1000

# Deactivate sculpting
sculpt_deactivate invalid

# make the backbone atoms free
flag fix, (bbone), clear

Or if your PyMOL installation “includes modelling capabilities” [1], you can get even better results with the clean command:

betafab2 clash, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL, (R)B3hL

# select the backbone -> makes a new selection (bbone)
select_bbb bbone, invalid

# fix the backbone atoms
flag fix, (bbone), set

# Geometry optimization
clean invalid

# make the backbone atoms free
flag fix, (bbone), clear

Graphical user interface

This plug-in supplies two GUI tools, available in the Plugin menu of the PyMOL main menu bar.

[1]In other words, if the freemol extension is installed. It is installed by default in the Incentive and the Education version of PyMOL, but it can also be made to work in the open source version.