XML to Pyrosetta: EvolutionaryDynamicsMover as an example

In the previous post I discuss the strategies to use a Pyrosetta class when the documentation lets you down. One topic discussed was the conversion of a Rosetta XML script to Pyrosetta. Here is an example, namely using the EvolutionaryDynamics mover as an example.

Pyrosetta scripting without a manual

I got recently asked how to figure out how to write a Pyrosetta script when there is no example. This is definitely the biggest weakness of Pyrosetta and Rosetta script, but it is not insurmountable. In fact, there is a wealth of information that is hidden that can be mined. Here is how and in the next post, I give an example.

Rosetta/Pyrosetta on a cluster or in the cloud

Due to licensing Rosetta and Pyrosetta cannot be installed via apt-get/pip but has to be downloaded from the Rosetta Commons website. This makes things harder if you are in a colabs notebook, ssh'ed into a machine or running off a remote jupyter notebook. Luckily it actually is straightforward.

Stay hydrated

Waters can be an integral part of a protein structure, in fact, it is common to find water crystallised tightly in an X-ray structure. These waters can change the calculated Gibbs free energy of a protein and give better experimental results. Explicit waters can be added in Rosetta/Pyrosetta thanks to the SPaDES algorithm described in Lai et al. 2017. Here is a guide to using it in Pyrosetta.

Love thy neighbours, but select them with caution

In Rosetta NeighborhoodResidueSelector behaves differently than PyMOL's expand selector and it is good to be aware of it. Namely, in PyMOL the distance is from any atom, while in Rosetta it is from the center of mass atom, unless specified differently. In reality CloseContactResidueSelector works like PyMOL's expand selector.

RDKit for Rosetta: PLP ligand space as an example

Docking requires a molecule to dock. Preparing a ligand is often tricky, especially if the ligand is complicated, such as PLP. PLP is an interesting cofactor as it catalyses the reaction while the protein chooses the ligand. It binds tightly to the active site via its phosphate and its pyridine ring, while the metabolite to be transformed forms a Schiff base with it. Therefore, one would think that it makes easy to explore chemistry space with it. However, several technical hurdles are encountered, making it quite didactic.

Everything you wanted to know about isopeptide bonds in Rosetta, but were too afraid to ask

Rosetta is great at predicting (with some accuracy) the energies of variant proteins, however, to make the most out of it with proteins with internal isopeptide bonds a few considerations are needed.

The curious case of fluorescein and implicit waters

I recently was asked a straightforward task: get the energy scores of a given protein by itself, conjugated with fluorescein maleimide and its ring opened form. Despite that, I failed miserably because of implicit waters playing odd tricks.
Given that it is of no real use, I am happy to share so to give a tutorial of how to do that in Rosetta (ligand docking), which I found taxing the first time.

Rosetta easteregg

The guide to use Rosetta may be a bit, ehm, flaky, but I think it is made up for by this rather amusing comment header I found in one of its Perl script, kudos to the author.

###############################################################################
#
# MAKE_FRAGMENTS.PL 1.00 -- THE (PEN)ULTIMATE IN HOME FRAGMENT-PICKING SOFTWARE!
#
# CAUTION:  NO USER SERVICEABLE PARTS BELOW!
#
#           TO REDUCE RISK OF ELECTRIC SHOCK, DO NOT REMOVE THE COVER!
#           DO NOT ATTEMPT REPAIRS!  REFER SERVICING TO YOUR AUTHORIZED DEALER!
#           AVOID PROLONGED EXPOSURE TO HEAT OR SUNLIGHT!
#           TO REDUCE THE RISK OF FIRE OR ELECTRIC SHOCK, DO NOT EXPOSE THE
#            PRODUCT TO RAIN AND/OR MOISTURE!
#           DO NOT MOVE THE PRODUCT WHILE IN USE!
#           DO NOT LOOK AT THE PRODUCT WHILE IN USE!
#           DO NOT COMPLAIN ABOUT THE PRODUCT WHILE IN USE!
#           DO NOT DISCUSS THE PRODUCT WHILE IN USE!
#           DO NOT THINK ABOUT THE PRODUCT WHILE IN USE!
#           CLEAN ONLY WITH MILD DETERGENTS AND A SOFT CLOTH!
#           USE ONLY IN WELL-VENTILATED AREAS!
#
#           FOR EXTERNAL USE ONLY!  DO NOT TAKE INTERNALLY!
#           MAY PRODUCE STRONG MAGNETIC FIELDS!
#
#           DO NOT REMOVE THIS TAG UNDER PENALTY OF LAW.
#
#           THIS ARTICLE CONTAINS NEW MATERIAL ONLY.
#
#           THIS LABEL IS AFFIXED IN COMPLAINCE WITH THE UPHOLSTERED AND
#            STUFFED ARTICLES ACT.
#
#
# (IN OTHER WORDS:  DON'T EVEN *THINK* ABOUT CHANGING THINGS BELOW THIS POINT!)
#
###############################################################################