Solvate and Run MD [MDPrep] [MDRun]

Description

  • Purpose:

    • This Floe performs MD simulations given one or more complete solutes as input, each to be treated in its entirety in a separate simulation.

  • Method Recommendations/Requirements:

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

    • Each solute can have multiple conformers but each conformer will be run separately.

    • The starting configuration should not have very high gradients, in particular no bad clashes.

    • Protein components need 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

    • The output produced by this Floe is not compatible with the Analyze Protein-Ligand MD Floe

    • 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:

    • Bound Protein-Ligand MD [MDPrep] [MD]

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

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

Each input solute is solvated to make a flask with periodic boundary conditions and parametrized according to the selected force fields. A minimization stage is performed on the flask followed by a warm up (NVT ensemble) and three equilibration stages (NPT ensemble). In the minimization, warm up and equilibration stages positional harmonic restraints are applied. At the end of the equilibration stages a production run (default 2ns) is performed on the unrestrained flask.

Promoted Parameters

Title in user interface (promoted name)

Solvation Parameters

Solution Density (density): Solution density in g/ml

  • Type: decimal

  • Default: 1.03

Salt Concentration (salt_concentration): Salt concentration (Na+, Cl-) in millimolar

  • Type: decimal

  • Default: 150.0

Restrain protein tumbling (restraint_protein_tumbling): Restraining protein tumbling allows for a smaller flask

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Restrain protein tumbling wt (restraint_protein_tumbling_Wt): Restraint weight for pre-defined xyz atom restraints in kcal/(mol A^2)

  • Type: decimal

  • Default: 0.1

CPU GPU Spot Policy Selection

CPUs (cpu_count_md): The number of CPUs to run this cube with

  • Type: integer

  • Default: 12

GPUs (gpu_count_md): The number of GPUs to run this cube with

  • Type: decimal

  • Default: 1

Spot policy (spot_policy_md): Control cube placement on spot market instances

  • Type: string

  • Default: Allowed

  • Choices: [‘Allowed’, ‘Preferred’, ‘NotPreferred’, ‘Prohibited’, ‘Required’]

MD Setup Parameters

Ligand Force Field (ligand_ff): Force field to be applied to the ligand. The OpenFF >=1.3.1 and Custom force fields may be augmented with bespoke force field parameters by turning on ‘Use Bespoke Parameters When Available’ and providing SMIRNOFF format parameters on the input record.

  • Required

  • Type: string

  • Default: OpenFF_2.2.0

  • Choices: [‘Gaff_1.81’, ‘Gaff_2.2.20’, ‘OpenFF_1.1.1’, ‘OpenFF_1.2.1’, ‘OpenFF_1.3.1’, ‘OpenFF_2.0.0’, ‘OpenFF_2.2.0’, ‘Smirnoff99Frosst’, ‘Custom’]

Custom Ligand Force Field File (custom_offxml_file_in): One or more SMIRNOFF XML files defining the force field to be applied to the ligand. This input is required when ‘Ligand Force Field’ is set to ‘Custom’.

  • Type: file_in

Protein Force Field (protein_ff): Force field to be applied to the protein.

  • Required

  • Type: string

  • Default: Amber14SB

  • Choices: [‘Amber14SB’, ‘Amber99SB’, ‘Amber99SBildn’, ‘AmberFB15’]

Cube max run time (cube_max_run_time): Max Cube Running Time in hrs

  • Type: decimal

  • Default: 1

MD Engine (md_engine): Select the available MD engine

  • Type: string

  • Default: OpenMM

  • Choices: [‘OpenMM’, ‘Gromacs’]

Hydrogen Mass Repartitioning (HMR): Give hydrogens more mass and increase the MD integration time step from 2 to 4 fs.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

NPT Production Runtime (prod_ns): NPT simulation production time in nanoseconds

  • Type: decimal

  • Default: 2.0

Trajectory Interval (prod_trajectory_interval):

Trajectory saving interval in nanoseconds. The default trajectory saving interval is 0.025 ns. For denser sampling, set the interval to 0.004 ns. For longer simulations, consider using an interval larger than the default setting, as smaller intervals substantially increase trajectory file sizes and associated AWS storage costs.

  • Type: decimal

  • Default: 0.025