index.rst

Welcome to the GPCRdb documentation

The GPCRdb contains data, diagrams and web tools for G protein-coupled receptors (GPCRs). Users can browse all GPCR crystal structures and the largest collection of receptor mutants. Diagrams can be produced and downloaded to illustrate receptor residues (snake-plot and helix box diagrams) and relationships (phylogenetic trees). Reference (crystal) structure-based sequence alignments take into account helix bulges and constrictions, display statistics of amino acid conservation and have been assigned generic residue numbering for equivalent residues in different receptors.

The source code and source data are freely available on GitHub.

Below, a table overview of all the different pages and functionalities in GPCRdb grouped by sections, along links to specific documentation pages, associated slides and video demonstrations.

SEQUENCES

Page name	Video	Slides	Demo	Reference	Short description
Sequence alignments				Isberg et al. NAR 2016 Kooistra et al. NAR 2021	Provides sequence alignment analyses of receptors.
Generic residue number tables				Isberg et al. TiPS 2015	Displays the generic residue number tables for the single or set of receptors selected.
Genetic variants				Hauser et al. Cell 2018	Section showing the variation coverage, single receptor variants and the estimated economic burden for drugs targeting GPCRs.
Isoforms				Marti-Solano et al. Nature 2020	Info page highlighting the number of unique isoforms detected for each receptor gene.

STRUCTURES

Page name	Video	Slides	Demo	Reference	Short description
Structure coverage				Isberg et al. NAR 2016	Overview of the structure information available in GPCRdb. Data is shown using detailed inforgraphics and plots.
Structures				Isberg et al. NAR 2014 Kooistra et al. NAR 2021	Browser page listing detailed information for all the structures present in GPCRdb.
Structure models				Pándy-Szekeres et al. NAR 2023	Browser page listing all the AlphaFold-Multistate generated homology models and refined structures present in GPCRdb.
Structure model validation				Kooistra et al. NAR 2021 Pándy-Szekeres et al. NAR 2023	Browser page listing the RMSD values comparing the latest model before a structure of the same receptor in the same state was published.

STRUCTURE ANALYSIS

Page name	Video	Slides	Demo	Reference	Short description
Structure comparison tool				Kooistra et al. Nat. Struct. Mol. Biol 2021	Interactive tool for investigation of single structures or comparison of sets of structures. The tool allows for more than 20 different plot representations and lists available contact position pairs.
Structure similarity trees				Kooistra et al. Nat. Struct. Mol. Biol 2021	Interactive tool showcasing the similarity trees of selected set of receptors. Generated trees can be further graphically tweaked and downloaded in high resolution format.
Structure superposition				Isberg et al. NAR 2016	Functionality designed for the superpositioning of user defined structures (reference and test), allowing segment based selection.
Generic residue numbering (PDB)				Isberg et al. NAR 2016 Isberg et al. TiPS 2015	GPCRdb generic number annotation of user uploaded PDB files where numbers get deposited in the B-factor column.

STRUCTURE CONSTRUCTS

Page name	Video	Slides	Demo	Reference	Short description
Construct/Experiment design				Munk et al. Nat. Methods 2019	Section for the design and alignment of experimental constructs and associated browser page listing experiments walkthrough.
Truncation/Fusion analysis				Munk et al. Nat. Methods 2019	Section with pages showing information about truncation sites fusion sites and deletion loops across the available GPCRdb data.
Mutation analysis				Munk et al. Nat. Methods 2019	Section with mutations oriented browsers, listing stabilizing mutations, substitution matrix and a dedicated stabilising mutation analyser.

DETERMINANTS & MUTATIONS

Page name	Video	Slides	Demo	Reference	Short description
Sequence signature tool				Kooistra et al. NAR 2021	Interactive tool for the investigation of sequence signature across two different user defined set of receptors.
State stabilizing mutation design				Kooistra et al. Nat. Struct. Mol. Biol 2021	Browser page listing detailed state stabilising mutation information for each receptor present in GPCRdb.

LIGANDS & BIOACTIVITIES

Page name	Video	Slides	Demo	Reference	Short description
Ligand coverage				Pándy-Szekeres et al. NAR 2018	Overview of the ligands information available in GPCRdb. Data is shown using detailed inforgraphics and plots.
Ligands				Pándy-Szekeres et al. NAR 2018 Pándy-Szekeres et al. NAR 2023	Section allowing the search for ligands associated to a specific receptor or using ligand name, database ID or chemical information (SMILES or Inchikey).

ENDOGENOUS LIGANDS

Page name	Video	Slides	Demo	Reference	Short description
Endogenous ligands				Pándy-Szekeres et al. NAR 2023	Browser page listing detailed information for endogenous ligands present in GPCRdb. Data are derived and maintained by Guide to Pharmacology.

DRUGS & AGENTS IN TRIAL

Page name	Video	Slides	Demo	Reference	Short description
Drugs targets and indicators				Hauser et al. Nat. Rev. Drug Discov 2017	Browser page listing information about drugs, their targets of action, therapeutic indication and clinical status with associated references.
Drug target tree				Hauser et al. Nat. Rev. Drug Discov 2017	Interactive infographic tree showing drug data information on established or under clinical trials GPCR targets.
Drug statistics				Hauser et al. Nat. Rev. Drug Discov 2017	Overview of the GPCR class as drug target, with focus on receptor family targets, drug molecule types, mode of action and disease indications.

LIGAND SITES

Page name	Video	Slides	Demo	Reference	Short description
GPCR-ligand interactions				Isberg et al. NAR 2016 Munk et al. COPHAR 2016	Functionality showing the protein-ligand interactions for the available PDB structures in GPCRdb using graphical representation and 3D visualization tools.
Site search				Isberg et al. NAR 2016	Section designed for the investigation of protein-ligand interactions of set of receptors, either using sequence motifs or ligand complex through a user defined PDB file.

LIGAND SITE MUTATIONS

Page name	Video	Slides	Demo	Reference	Short description
Mutation coverage				Munk et al. COPHAR 2016	Overview of the mutations information available in GPCRdb. Data is shown using detailed inforgraphics.
Mutations				Munk et al. COPHAR 2016	Browser page listing mutations for user selected receptors and protein segments. Result table also provides information about ligand affinity for the mutation (FoldChange) if available.
Mutation design tool				Munk et al. COPHAR 2016	Section with mutation design tool based either on a PDB code or receptor name. Result page lists suggested mutations with associated structure interactions, supporting ligands, receptors and mutagenesis experiments.
Mutation data submission				Munk et al. COPHAR 2016	Description to the mutation data submission form and guidelines on how to submit your experimental data to GPCRdb.

The documentation is organised into three sections:

• :ref:`user-docs`
• :ref:`dev-docs`
• :ref:`about-docs`

.. toctree::
    :maxdepth: 2
    :caption: User documentation

    receptors
    ligands
    signalproteins
    sequences
    sequence_signature
    structures
    structure_comparison
    constructs
    mutations
    biasedsignaling
    sites
    generic_numbering
    drugs
    nhs
    variants

.. toctree::
    :maxdepth: 2
    :caption: Developer documentation

    web_services
    contributing
    local_installation
    coding_style
    git_workflow
    reload_database
    building_a_database

.. toctree::
    :maxdepth: 2
    :caption: About GPCRdb

    about
    contact
    contributors
    citing
    acknowledgements
    legal_notice
    meetings
    linking
    external_sites