Structure comparison examples

OpenStructure provides "actions" for general benchmarking use cases.

• compare-structures: Focuses on comparisons involving polymer entities, i.e. protein, DNA and RNA chains
• compare-ligand-structures: Focuses on comparisons of interactions between polymer entities and non-polymer entities, i.e. small molecule ligands

Before doing any scoring

Pull example data from the repository:

wget https://git.scicore.unibas.ch/schwede/openstructure/-/archive/master/openstructure-master.zip?path=examples/scoring -O example.zip
unzip -j example.zip

Run the examples

The example commands here assume an OpenStructure installation (compile instructions: https://openstructure.org/docs/install/). Running the computations in containers provide a considerably easier setup than compiling OpenStructure from source. Instructions for setup and running equivalent computations are available for

• Docker
• Singularity

A detailed list of options can be found in the action documentation. Alternatively, the commands

ost compare-structures -h
ost compare-ligand-structures -h

will list all available options of the respective action. Both actions compute scores on an “opt-in” basis and produce output in JSON format. Example to compute global and per-residue LDDT scores, as well as as QS-scores which are written to default output (out.json):

ost compare-structures -m model.pdb -r reference.cif.gz --lddt --local-lddt --qs-score

Results should be computed within seconds and example output can be found here. We refer to the action documentation for in-depth description of the provided data items.

By default, model-reference chains are aligned using Needleman-Wunsch. Many benchmarking efforts such as CASP and CAMEO assume residue numbers according to target sequence(s). Both "actions" allow to derive model-reference chain alignments according to these numbers which should be preferred in these cases. This can be enabled by adding a -rna (residue number alignment) flag:

ost compare-structures -m model.pdb -r reference.cif.gz --lddt --local-lddt --qs-score -rna

The same example also contains small molecule ligands. We can compute LDDT-PLI and BiSyRMSD with:

ost compare-ligand-structures -m model.pdb -r reference.cif.gz -ml *.sdf --rmsd --lddt-pli

Results should be computed within seconds and example output can be found here. We refer to the action documentation for in-depth description of the provided data items.

Again, it is advised to use the -rna flag if applicable. In this example, reference ligands are directly extracted from the provided mmCIF file based on "non-polymer" entity types. This only works in case of mmCIF input AND if the respective ligand is in the PDB component dictionary which defines connectivity (matching based on compound name). Container solutions come with such a dictionary which has been created at build time. Check the Docker/Singularity instructions linked above on how to set the latest dictionary, i.e. "Compound Library". You can override automatic extraction by providing SDF files with ligand coordinates and connectivity information. If the receptor is provided in PDB format, ligands must be provided in SDF format.

Docker

For complete documentation on using Docker with OpenStructure, click here. This section provides a quick-start guide to help you get up and running with scoring using Docker. Most docker installations require you to add sudo in front of the following commands.

Get the latest Docker image from the OpenStructure registry:

docker pull registry.scicore.unibas.ch/schwede/openstructure:latest

run one of the scoring examples, other examples need to be adapted accordingly:

docker run --rm -v $(pwd):/home registry.scicore.unibas.ch/schwede/openstructure:latest compare-structures -m model.pdb -r reference.cif.gz --lddt --local-lddt --qs-score

Singularity

For complete documentation on using Singularity with OpenStructure, click here. This section provides a quick-start guide to help you get up and running with scoring using Singularity.

Building the singularity container requires root permissions:

wget https://git.scicore.unibas.ch/schwede/openstructure/-/raw/master/singularity/Singularity
sudo singularity build ost.img Singularity

run one of the scoring examples, other examples need to be adapted accordingly:

singularity run --app OST ost.img compare-structures  -m model.pdb -r reference.cif.gz --lddt --local-lddt --qs-score