Molecular Interaction Potentials (CMIP)

Classical molecular interaction potentials with CMIP: MIP grids and water/ion titration for a protein, protein-ligand (EGFR-Erlotinib) and protein-protein (RBD-hACE2) interaction energies.

by Temple Compute

Run Molecular Interaction Potentials (CMIP) on Horus

W-22 · Classical Molecular Interaction Potentials

Classical molecular interaction potentials with CMIP: MIP grids and water/ion titration for a protein, protein-ligand (EGFR-Erlotinib) and protein-protein (RBD-hACE2) interaction energies.

Domain: BioExcel Building Blocks

Overview

Classical Molecular Interaction Potentials (CMIP) with three independent case studies: MIP grids and water/ion titration on a protein (default lysozyme, 1AKI), protein-ligand interaction energies for a PDB complex (default EGFR-Erlotinib, 4HJO with ligand AQ4; ligand parameterized with ACPype/GAFF and minimized with AMBER), and protein-protein interaction energies between two chains of a pre-run AMBER structure (default SARS-CoV-2 RBD-hACE2). The workflow has 29 tasks.

Pipeline

Case 1, protein MIP and titration
fetch_pdb_lysozyme -> cmip_prepare_pdb_lysozyme  Fetch or upload the MIP protein, add CMIP charges
cmip_titration_lysozyme -> cat_pdb_titration     Structural waters and ions
cmip_run_mip_pos / _neg / _neutral               MIP grids

Case 2, protein-ligand complex
fetch_pdb_complex -> remove_pdb_water -> extract_heteroatoms -> reduce_add_hydrogens -> acpype_params_ac
leap_gen_top -> sander_mdrun -> amber_to_pdb     Topology, minimization
cmip_prepare_structure_complex -> remove_ligand  CMIP charges, isolated protein
cmip_ignore_residues_protein -> cmip_run_egfr_interaction   Mask all non-ligand residues, ligand-protein energies

Case 3, protein-protein complex (partners A and B)
cmip_prepare_structure_md -> extract_chain_hace2 (A) / extract_chain_rbd (B)
cmip_run_rbd_box / cmip_run_hace2_box / cmip_run_complex_box
cmip_ignore_residues_rbd -> cmip_run_rbd_interaction       Partner B vs partner A
cmip_ignore_residues_hace2 -> cmip_run_hace2_interaction   Partner A vs partner B

Inputs / Outputs

Outputs (results/):

protein.*.pdb, protein.mip_{pos,neg,neutral}.cube: MIP protein preparation, titration and MIP grids
complex.pdb, complex.noHOH.pdb, ligand*.pdb, ligand_params.*, structure.*: complex, ligand parameters, AMBER topology and minimized complex
complex.cmip.pdb, complex.noLIG.pdb, complex.Prot_ignored.cmip.pdb: CMIP-ready complex, isolated protein, masked complex
complex.energies.log, complex.ener.byat.out: protein-ligand interaction energies
pp_complex.*.cmip.pdb, partner_{a,b}.cmip.pdb, {partner_a,partner_b,pp_complex}.box.json: CMIP-ready complex, split chains and grid boxes
partner_{a,b}.energies.log, partner_{a,b}.energies.byat.out: protein-protein interaction energies

Parameters

| id | Default | Meaning | |---|---|---| | pdb_id | 1aki | Case 1 PDB code; leave empty to use structure. | | structure | examples/1aki.pdb | Case 1 PDB file used when pdb_id is empty. | | titration_waters | 20 | Water molecules placed by the titration (0-500). | | titration_ions | 5 | Positive and negative ions placed by the titration, same count each (0-100). | | complex_pdb_id | 4hjo | Case 2 PDB code of the protein-ligand complex (EGFR-Erlotinib). | | complex_ligand | AQ4 | Case 2 ligand residue name (Erlotinib); every other residue is masked as protein for the interaction energy. | | complex_ligand_charge | 0 | Case 2 ligand net charge passed to ACPype (-20 to 20). | | md_pdb | Files/RBD-hACE2-ZN.pdb | Case 3 AMBER structure of a two-chain complex; must match md_top. | | md_top | Files/RBD-hACE2-ZN.top | Case 3 AMBER topology matching md_pdb. | | partner_a_chain | A | Case 3 chain of the first partner (hACE2). | | partner_b_chain | B | Case 3 chain of the second partner (RBD). |