#!/usr/bin/env nextflow
nextflow.enable.dsl=2

params.protein1_fasta = '/omic/eureka/bioemu/input/trp_cage.fasta'
params.protein2_fasta = '/omic/eureka/bioemu/input/villin_headpiece.fasta'
params.complex_name = 'protein_complex'
params.exp_dG = -10.0
params.outdir = '/omic/eureka/bioemu/output'
params.cache_dir = '/tmp/bioemu_cache'
params.num_samples = 10
params.batch_size = 5
params.temperature = 300
params.n_clusters = 5

process GENERATE_STRUCTURE_1 {
    container 'harbor.cluster.omic.ai/omic/bioemu:latest'
    publishDir "${params.outdir}/${params.complex_name}/protein1", mode: 'copy'

    input:
        path fasta

    output:
        path "protein1_topology.pdb", emit: topology
        path "protein1_samples.xtc", emit: samples

    script:
    """
    SEQUENCE=\$(grep -v ">" ${fasta} | tr -d '\\n')
    mkdir -p ${params.cache_dir}

    python3 -m bioemu.sample \\
        --sequence "\${SEQUENCE}" \\
        --num_samples ${params.num_samples} \\
        --batch_size_100 ${params.batch_size} \\
        --output_dir . \\
        --cache_embeds_dir ${params.cache_dir}

    mv topology.pdb protein1_topology.pdb
    mv samples.xtc protein1_samples.xtc
    """
}

process GENERATE_STRUCTURE_2 {
    container 'harbor.cluster.omic.ai/omic/bioemu:latest'
    publishDir "${params.outdir}/${params.complex_name}/protein2", mode: 'copy'

    input:
        path fasta

    output:
        path "protein2_topology.pdb", emit: topology
        path "protein2_samples.xtc", emit: samples

    script:
    """
    SEQUENCE=\$(grep -v ">" ${fasta} | tr -d '\\n')
    mkdir -p ${params.cache_dir}

    python3 -m bioemu.sample \\
        --sequence "\${SEQUENCE}" \\
        --num_samples ${params.num_samples} \\
        --batch_size_100 ${params.batch_size} \\
        --output_dir . \\
        --cache_embeds_dir ${params.cache_dir}

    mv topology.pdb protein2_topology.pdb
    mv samples.xtc protein2_samples.xtc
    """
}

process CALCULATE_BINDING {
    container 'harbor.cluster.omic.ai/omic/bioemu:latest'
    publishDir "${params.outdir}/${params.complex_name}/analysis", mode: 'copy'

    input:
        path protein1_topology
        path protein1_samples
        path protein2_topology
        path protein2_samples

    output:
        path "binding_energy.csv"
        path "binding_energy_report.txt"
        path "energy_comparison.png"

    script:
    """
    python3 /opt/bioemu/scripts/calculate_binding.py \\
        --protein1_topology ${protein1_topology} \\
        --protein1_samples ${protein1_samples} \\
        --protein2_topology ${protein2_topology} \\
        --protein2_samples ${protein2_samples} \\
        --temperature ${params.temperature} \\
        --n_clusters ${params.n_clusters} \\
        --output binding_energy.csv \\
        --plot energy_comparison.png

    echo "# Binding Free Energy Analysis: ${params.complex_name}" > binding_energy_report.txt
    echo "Experimental: ${params.exp_dG} kcal/mol" >> binding_energy_report.txt
    PREDICTED_DG=\$(grep -A1 "binding_free_energy" binding_energy.csv | tail -n1 | cut -d',' -f2)
    echo "Predicted: \${PREDICTED_DG} kcal/mol" >> binding_energy_report.txt
    """
}

workflow {
    fasta1 = Channel.fromPath(params.protein1_fasta)
    fasta2 = Channel.fromPath(params.protein2_fasta)

    GENERATE_STRUCTURE_1(fasta1)
    GENERATE_STRUCTURE_2(fasta2)

    CALCULATE_BINDING(
        GENERATE_STRUCTURE_1.out.topology,
        GENERATE_STRUCTURE_1.out.samples,
        GENERATE_STRUCTURE_2.out.topology,
        GENERATE_STRUCTURE_2.out.samples
    )
}