Solvate and Run MD

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Product-based/Molecular Dynamics/GROMACS

  • Product-based/Molecular Dynamics/OpenMM

  • Role-based/Computational Chemist

  • Role-based/Medicinal Chemist

  • Task-based/Molecular Dynamics

  • Solution-based/Hit to Lead/Target Preparation/Generic MD simulation

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

    • Short Trajectory MD with Analysis

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 2 ns) is performed on the unrestrained flask.

Promoted Parameters

Title in user interface (promoted name)

Inputs

Solute Input Dataset (solute): Solute input file or dataset

  • Required

  • Type: data_source

Outputs

MD Output Dataset (md_out): Output dataset of MD simulations.

  • Required

  • Type: dataset_out

  • Default: md_output

MD Recovery Output Dataset (md_recovery_out): This is an optional MD recovery dataset generated when the ‘Save MD recovery records’ parameter of the ‘MD Recovery Switch’ cube is ‘On’.

  • Required

  • Type: dataset_out

  • Default: md_recovery

Trajectory Downloader (traj_downloader): Title for the trajectory downloader floe report.

  • Type: string

  • Default: Trajectory Downloader

Failed Output Dataset (fail_out): Output dataset of failed calculations.

  • Required

  • Type: dataset_out

  • Default: Failed Output for Solvate and Run MD

Solvation Parameters

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

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Restrain Protein Tumbling Weight (restraint_protein_tumbling_Wt): Restraint weight for predefined xyz atom restraints in kcal/(mol Å2).

  • Type: decimal

  • Default: 0.1

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

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_2.2.1

  • 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’, ‘OpenFF_2.2.1’, ‘Smirnoff99Frosst’, ‘Custom’]

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

  • Required

  • Type: string

  • Default: Amber14SB

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

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

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_bn_ns): NPT simulation production time in nanoseconds

  • Type: decimal

  • Default: 2.0

Trajectory Interval (prod_trajectory_interval): Trajectory saving interval in nanoseconds

  • Type: decimal

  • Default: 0.025

CPU, GPU, Spot Policy Selection

AWS Spot Instances for MD Cubes (spot_policy_md): Set the AWS Spot Policy just for the MD cubes

  • Type: string

  • Default: Allowed

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

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

  • Type: integer

  • Default: 4

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

  • Type: decimal

  • Default: 1