Protein-Ligand MM/PBSA Workflow (Execution-Ready)

Note:

• Local files are not directly accessible by the server. Please upload them to the server using molclaw-file-transfer before execution.
• For PDB file inputs, it is recommended to preprocess them using molclaw-pdbfixer before execution.
• Please refer to skill molclaw-scp-server to complete tool invocation.

Canonical Toolchain

1. fix_pdb → cleans the receptor and returns output_file.
2. prepare_complex → consumes the repaired protein plus ligand to build the MD workspace and writes output_dir.
3. run_mmpbsa → consumes work_dir to execute GB/PB calculations and emits CSV summaries.
4. analyze_mmpbsa (optional) → consumes run_mmpbsa.output_dir to derive plots/reports from the MM/PBSA results.

SCP Tool Names (must use)

• fix_pdb
• prepare_complex
• run_mmpbsa
• analyze_mmpbsa

Tool References

• fix_pdb: reference_fix_pdb.md
• prepare_complex: reference_prepare_complex.md
• run_mmpbsa: reference_run_mmpbsa.md
• analyze_mmpbsa: reference_analyze_mmpbsa.md

Data Handover Contract

1. fix_pdb.output_file → prepare_complex.protein (never substitute with manual paths).
2. prepare_complex.output_dir → run_mmpbsa.work_dir (required to contain em.gro, md.xtc, md.tpr, topol.top, ligand files).
3. run_mmpbsa.output_dir → analyze_mmpbsa.work_dir when analysis is enabled.

Step Details

Step 1: fix_pdb

• Pre-flight checks: ensure input_path exists and is a readable PDB; dry_run defaults to False so the file is written unless explicitly skipping.
• Inputs: input_path, add_hydrogens, remove_water, replace_nonstandard, add_missing_residues, dry_run.
• Optional stage: set keep_chains to restrict the repair when a subset of chains is needed.
• Success criteria: status == "success", output_file is populated, atom/residue counts report >0.
• Fallback hints: replay the msg, mention which residue/chain failed, or rerun with dry_run=True to diagnose before writing.

Step 2: prepare_complex

• Pre-flight checks: confirm protein equals fix_pdb.output_file, ligand path exists, and any pose index is valid within the ligand file.
• Inputs: protein, ligand, pose, gpu_ids, full_md, nvt_time, npt_time, md_time, ph.
• Optional stage: short circuits such as full_md=False for quick workspace generation, but then downstream steps must adjust expectations.
• Success criteria: status == "success", output_dir is non-empty, files contains em.gro/md.xtc/topol.top.
• Fallback hints: if GPU resources are oversubscribed, rerun with gpu_ids trimmed or full_md=False; if ligand conversion fails, switch to .mol2 or .pdb input.

Step 3: run_mmpbsa

• Pre-flight checks: work_dir exists and matches prepare_complex.output_dir; verify expected em.gro, md.xtc, and topol.top exist before invoking.
• Inputs: work_dir, method (gb/pb/both), nproc, interval, startframe, endframe, generate_input, dry_run.
• Optional stage: method controls whether GB, PB, or both runs execute; dry_run=True tests configuration without executing heavy compute.
• Success criteria: status == "success", gb_dir or pb_dir is created, results dictionary contains energy estimates, required CSVs (FINAL_RESULTS.csv) exist.
• Fallback hints: on missing CSVs, check nproc limits or re-run with generate_input=True; if dry_run was left True, rerun with the actual run.

Step 4: analyze_mmpbsa (optional)

• Pre-flight checks: enable_analysis flag True and work_dir equals run_mmpbsa.output_dir; confirm the CSV outputs are present.
• Inputs: work_dir.
• Optional stage: no extra per-file overrides are required in normal workflow usage.
• Success criteria: status == "success", output_dir exists, reports dictionary lists generated PNG/CSV/MD artifacts.
• Fallback hints: treat analyzer failures as soft; log the msg and keep the run_mmpbsa results as the primary output.

Agent Flow

1. Protein repair → complex build: fix_pdb.output_file feeds prepare_complex.protein, guaranteeing the complex uses the cleaned receptor.
2. Workspace build → free-energy run: prepare_complex.output_dir becomes run_mmpbsa.work_dir, producing both mmgbsa/FINAL_RESULTS.csv and mmpbsa/FINAL_RESULTS.csv depending on method.
3. Optional analysis: when enabled, the analyzer consumes run_mmpbsa.output_dir (work_dir) to assemble summary plots, which are then surfaced through analyze_mmpbsa.output_dir and reports.
4. Normalized insights: every branch funnels into the same work_dir CSV artifacts so downstream agents can compare GB, PB, and analyzer outputs uniformly.

Normalized Outputs (per workflow)

• fix_pdb: output_file (cleaned receptor).
• prepare_complex: output_dir/files (workspace containing GROMACS artifacts).
• run_mmpbsa: work_dir, gb_dir, pb_dir, results, command.
• analyze_mmpbsa: output_dir, reports, detected_mode, missing_files (optional insights).

Safety Checklist

• Never pass manual MD files instead of prepare_complex.output_dir.
• Treat any missing output_file/output_dir as a hard failure and stop before the next tool.
• Validate GPU/CPU resources before running long run_mmpbsa jobs (nproc, gpu_ids).
• If method="both", ensure both PB and GB CSVs are created; otherwise, rerun with method="pb" or "gb" only.
• Surface actionable diagnostics (missing file, invalid pose, transport error) in the msg field.