Boltz Pulldown

An experimental AlphaPulldown-like protocol using Boltz for multimer predictions.

Overview

Boltz Pulldown runs multimer predictions from sequence for all target-binder pairs, allowing you to assess binding interactions between multiple potential interaciton partners.

Command-line Options

See available options with --help:

nextflow run boltz_pulldown.nf --help

Multiple Sequence Alignments (MSAs)

By default, no MSAs are used. To enable:

  • --create_target_msa=true: Generate MSAs for targets
  • --create_binder_msa=true: Generate MSAs for binders

⚠️ For de novo designed binders, use --create_target_msa=true to improve target prediction accuracy, but skip generating binder MSAs (--create_binder_msa=false, the default) as these are less informative since no homologs exist.

MSA Generation Options

Option 1: Remote Server

--use_msa_server

Uses the remote ColabFold mmseqs2 server.

Option 2: Local Databases

Download and set up databases with the ColabFold setup_databases.sh script, then specify paths:

--uniref30 /path/to/uniref30
--colabfold_envdb /path/to/colabfold_envdb

Custom Boltz Arguments

Add extra Boltz command-line arguments via ext.args in nextflow.config:

process {
    withName: BOLTZ {
        accelerator = 1
        time = 2.hours
        memory = '8g'
        cpus = 2

        // Example: CPU-only mode
        ext.args = "--accelerator cpu"
    }
}

Output

Default output directory: results/boltz_pulldown/

Includes:

  • Boltz predictions with scores and structures
  • boltz_pulldown.tsv - summary table
  • boltz_pulldown_report.html - report with statistics and ipTM score plots