Bound Protein-Ligand MD [MDPrep] [MDRun]

  • Purpose:

    • This Floe performs MD simulations given a prepared protein and a set of posed and prepared ligands.

  • Method Recommendations/Requirements:

    • The ligands need to have reasonable 3D coordinates, all atoms, and correct chemistry (in particular bond orders and formal charges).

    • Each ligand can have multiple conformers but each conformer will be run separately as a different ligand.

    • The starting poses should not have very high gradients, in particular no bad clashes with the protein.

    • The protein needs to be prepared to MD standards: protein chains must be capped, all atoms in protein residues (including hydrogens) must be present, and missing protein loops resolved or capped.

    • Crystallographic internal waters should be retained where possible.

  • Limitations

    • Currently this floe cannot handle covalent bonds between different components such as ligand, protein, and cofactors.

    • Glycosylation on proteins is truncated and the amino acid is capped with H.

  • Expertise Level:

    • Regular/Intermediate/Advanced

  • Compute Resource:

    • Depends on simulation length; Minimal resources for default 2 ns.

  • Keywords:

    • MD, MDPrep

  • Related Floes:

    • Short Trajectory MD with Analysis [MDPrep] [MD]

    • Ligand Bound and Unbound Equilibration for NES [MDPrep] [MD]

Given the inputs of the protein and posed ligands, the complex is formed with each ligand/conformer separately, and the complex is solvated and parametrized according to the selected force fields. A minimization stage is performed on the system followed by a warm up (NVT ensemble) and several equilibration stages (NPT ensemble). In the minimization, warm up, and equilibration stages, positional harmonic restraints are applied on the ligand and protein. At the end of the equilibration stages a production run (by default only 2 ns) is performed on the unrestrained system. The trajectory and final state are written out in the results record; no analysis is performed.

Promoted Parameters

  • flask_title (string) : Prefix name used to identify the Protein. If not specified, it will use the title of the input protein.
    Default: “”
  • HMR (boolean) : On enables Hydrogen Mass Repartitioning. Not currently implemented in Gromacs
    Default: True
  • md_engine (string) : Select the MD available engine
    Default: OpenMM
    Choices: OpenMM, Gromacs
  • cpu_count_md (integer) : The number of CPUs to run this cube with
    Default: 16 Min: 1 Max: 128
  • gpu_count_md (integer) : The number of GPUs to run this cube with
    Default: 1 Max: 16
  • spot_policy_md (string) : Control cube placement on spot market instances
    Default: Allowed
    Choices: Allowed, Preferred, NotPreferred, Prohibited, Required
  • out (dataset_out) : MD Dataset out
  • charge_ligands (boolean) : Assign ligand partial charges or not
    Default: True
  • protein (data_source) : Protein Dataset
  • max_md_runs (integer) : The maximum allowed number of MD runs
    Default: 500
  • n_md_starts (integer) : The number of MD starts for each ligand/conformer
    Default: 1
  • protein_ff (string) : Force field parameters to be applied to the protein
    Default: Amber14SB
    Choices: Amber14SB, Amber99SB, Amber99SBildn, AmberFB15
  • ligand_ff (string) : Force field to be applied to the ligand
    Default: OpenFF_2.0.0
    Choices: Gaff_1.81, Gaff_2.11, OpenFF_1.1.1, OpenFF_1.2.1, OpenFF_1.3.1, OpenFF_2.0.0, Smirnoff99Frosst
  • prod_ns (decimal) : Length of MD run in nanoseconds
    Default: 2.0
  • prod_trajectory_interval (decimal) : Trajectory saving interval in nanoseconds
    Default: 0.004
  • fail (dataset_out) : MD Dataset Failures out
  • ligands (data_source) : Ligand Dataset

Extra Required Parameters

  • Log Field (Field Type: String) : The field to store messages to floe report
    Default: Log Field
  • Log Field (Field Type: String) : The field to store messages to floe report
    Default: Log Field
  • Log Field (Field Type: String) : The field to store messages to floe report
    Default: Log Field