Package: alphapulldown
AlphaPulldown🥳 AlphaPulldown has entered the era of version 1.xWe have brought some exciting useful features to AlphaPulldown and updated its computing environment.AlphaPulldown is a Python package that streamlines protein-protein interaction screens and high-throughput modelling of higher-order oligomers using AlphaFold-Multimer:provides a convenient command line interface to screen a bait protein against many candidates, calculate all-versus-all pairwise comparisons, test alternative homo-oligomeric states, and model various parts of a larger complexseparates the CPU stages (MSA and template feature generation) from GPU stages (the actual modeling)allows modeling fragments of proteins without recalculation of MSAs and keeping the original full-length residue numbering in the modelssummarizes the results in a CSV table with AlphaFold scores, pDockQ and mpDockQ, PI-score, and various physical parameters of the interfaceprovides a Jupyter notebook for an interactive analysis of PAE plots and models🆕 integrates cross-link mass spec data with AlphaFold predictions viaAlphaLink2models🆕 able to integrate experimental models into AlphaFold pipeline using custom multimeric databasesPre-installationCheck if you have downloaded necessary parameters and databases (e.g. BFD, MGnify etc.) as instructed inAlphFold's documentation. You should have a directory like below:alphafold_database/                             # Total: ~ 2.2 TB (download: 438 GB)
   bfd/                                   # ~ 1.7 TB (download: 271.6 GB)
       # 6 files.
   mgnify/                                # ~ 64 GB (download: 32.9 GB)
       mgy_clusters_2018_12.fa
   params/                                # ~ 3.5 GB (download: 3.5 GB)
       # 5 CASP14 models,
       # 5 pTM models,
       # 5 AlphaFold-Multimer models,
       # LICENSE,
       # = 16 files.
   pdb70/                                 # ~ 56 GB (download: 19.5 GB)
       # 9 files.
   pdb_mmcif/                             # ~ 206 GB (download: 46 GB)
       mmcif_files/
           # About 180,000 .cif files.
       obsolete.dat
   pdb_seqres/                            # ~ 0.2 GB (download: 0.2 GB)
       pdb_seqres.txt
   small_bfd/                             # ~ 17 GB (download: 9.6 GB)
       bfd-first_non_consensus_sequences.fasta
   uniclust30/                            # ~ 86 GB (download: 24.9 GB)
       uniclust30_2018_08/
           # 13 files.
   uniprot/                               # ~ 98.3 GB (download: 49 GB)
       uniprot.fasta
   uniref90/                              # ~ 58 GB (download: 29.7 GB)
       uniref90.fastaCreate Anaconda environmentFirstly, installAnacondaand create AlphaPulldown environment, gathering necessary dependenciescondacreate-nAlphaPulldown-comnia-cbioconda-cconda-forgepython==3.10openmm==8.0pdbfixer==1.9kalign2cctbx-basepytestimportlib_metadatahhsuiteOptionally, if you do not have it yet on your system, installHMMERfrom AnacondasourceactivateAlphaPulldown
condainstall-cbiocondahmmerThis usually works, but on some compute systems users may wish to use other versions or optimized builds of already installed HMMER and HH-suite.Installation using pipActivate the AlphaPulldown environment and install AlphaPulldownsourceactivateAlphaPulldown

python3-mpipinstallalphapulldown==1.0.3
pipinstalljax==0.4.23jaxlib==0.4.23+cuda11.cudnn86-fhttps://storage.googleapis.com/jax-releases/jax_cuda_releases.htmlFor older versions of AlphaFold:
If you haven't updated your databases according to the requirements of AlphaFold 2.3.0, you can still use AlphaPulldown with your older version of AlphaFold database. Please follow the installation instructions on thededicated branchHow to developFollow the instructions atDeveloping guidelinesManualsAlphaPulldown supports four different modes of massive predictions:pulldown- to screen a list of "bait" proteins against a list or lists of other proteinsall_vs_all- to model all pairs of a protein listhomo-oligomer- to test alternative oligomeric statescustom- to model any combination of proteins and their fragments, such as a pre-defined list of pairs or fragments of a complexAlphaPulldown will return models of all interactions, summarize results in a score table, and will provide aJupyternotebook for an interactive analysis, including PAE plots and 3D displays of models colored by chain and pLDDT score.ExamplesExample 1 is a case wherepulldownmode is used. Manual:example_1Example 2 is a case wherecustomandhomo-oligomermodes are used. Manual:example_2Example 3 is demonstrating the usage of multimeric templates for guiding AlphaFold predictions. Manual:example_3all_vs_allmode can be viewed as a special case of thepulldownmode thus the instructions of this mode are added as Appendix in both manuals mentioned above.CitationsIf you use this package, please cite as the following:@Article{AlphaPUlldown,author={DingquanYu,GrzegorzChojnowski,MariaRosenthal,andJanKosinski},journal={Bioinformatics},title={AlphaPulldown—apythonpackageforprotein–proteininteractionscreensusingAlphaFold-Multimer},year={2023},volume={39},issue={1},doi={https://doi.org/10.1093/bioinformatics/btac749}}