.. HIPPO documentation master file, created by
   sphinx-quickstart on Wed Mar 13 16:27:26 2024.
   You can adapt this file completely to your liking, but it should at least
   contain the root `toctree` directive.

===================
HIPPO Documentation
===================

*Hit Interaction Profiling for Procurement Optimisation* (HIPPO) is a chemical database and python toolkit to expedite fragment-based drug discovery.

Installation
============

On Mac OS and Linux it is recommended to install from PyPI using Conda/Miniconda. 

Chemicalite is not supported on Windows, but there is a workaround described in the :doc:`windows`.

The `hippo` python module can be obtained from PyPI:

::
   
   $ pip install --upgrade hippo-db

You will also need `chemicalite` which is an extension to SQLite for cheminformatics:

::

   $ conda install -c conda-forge chemicalite=2024.05.1

N.B. Compatibility between rdkit and chemicalite versions is quite strict, and database files created with a certain version pair may not be interoperable with others. 

See also :ref:`installation-snippets`.

Getting started
===============

HIPPO uses an sqlite database with several inter-connected tables and Python-class representations thereof, the core concepts are explained in :doc:`definitions`. Once familiar you can try :doc:`getting_started`.


.. toctree::
   :maxdepth: 1
   :caption: Documentation Pages

   Home <self>

   Definitions, units, and data types <definitions>

   Getting started <getting_started>

   Adding data <add_data>

   Interfacing with Syndirella <syndirella>
   
   Running an FFF campaign <fff>
   
   Preparing files for Fragalysis upload <fragalysis>

   Windows installation <windows>

   Random recipe generation <rgen>

   API Reference <api_reference>

Core concepts
=============

HIPPO uses an sqlite database with several inter-connected tables (see :doc:`db`). In both the database and the python API the following core objects are defined:

Compound
--------

A :class:`.Compound` represents a ligand/small molecule with stereochemistry removed and no atomic coordinates. I.e. it represents the chemical structure. It's name is always an InChiKey. If a compound is an elaboration it can have a :meth:`.Compound.scaffold` property which is another :class:`.Compound`. :class:`.Compound` objects are target-agnostic and can be linked to any number of catalogue entries (:class:`.Quote`) or synthetic pathways (:class:`.Reaction`). 

Pose
----

A :class:`.Pose` is a particular conformer of a :class:`.Compound` within a protein environment. A pose will have its own (stereochemical) smiles string, and must have a path to a coordinate file. Poses can have *inspirations* that can be used to trace fragment-derived scaffolds in merges and expansions.

Reaction
--------

A :class:`.Reaction` is a simplified representation of a synthetic pathway to create a product :class:`.Compound`. Reactants (also :class:`.Compound` objects) as well as a reaction type are required.

See :doc:`definitions` for more detail.

.. _installation-snippets:

Installation Snippets
---------------------

If the above fails in your existing software environments, try this:

::
   
   mamba create --name py312 python=3.12
   mamba activate py312
   pip install hippo-db syndirella typer neo4j black gemmi
   mamba install chemicalite=2024.05.1 pdbfixer
   python -c  "import mrich; mrich.patch_rich_jupyter_margins()"

Additionally, this Dockerfile can be used to create a container with a Jupyter Notebook server:

::

   FROM quay.io/jupyter/minimal-notebook:2025-04-14
   LABEL authors="Max Winokan"
       
   # Upgrade pip and install JupyterLab
   RUN pip install --upgrade pip && pip install hippo-db syndirella typer neo4j black gemmi

   RUN mamba install --yes \
       chemicalite=2024.05.1 pdbfixer && \
       mamba clean --all -f -y && \
       fix-permissions "${CONDA_DIR}" && \
       fix-permissions "/home/${NB_USER}"

   # patch rich
   RUN python -c "import mrich; mrich.patch_rich_jupyter_margins()"

   # notebooks
   USER 0
   RUN mkdir "/home/code" && chown ${NB_USER} "/home/code" && \
       sudo apt update && sudo apt install screen -y
   USER ${NB_USER}

   # HIPPO dev branch
   WORKDIR "/home/code"
   RUN git clone https://github.com/mwinokan/HIPPO
   WORKDIR "/home/code/HIPPO"
   RUN git checkout dev && pip install -e . --no-deps

   EXPOSE 8888

   WORKDIR "/home/${NB_USER}"


.. Indices and tables
.. ==================

.. * :ref:`genindex`
.. * :ref:`modindex`
.. * :ref:`search`

.. Structure-based searching <queries>
.. Inserting synthetic pathways <insert_reactions>
.. Quoting with Pycule <pycule_tutorial>