Bound Protein-Ligand MD [MDPrep] [MDRun]

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


  • 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

Title in user interface (promoted name)


Protein Input Dataset (protein): Protein Input Dataset

  • Type: data_source

Ligand Input Dataset (ligands): Ligands-only input dataset or protein-ligand input dataset containing Design Unit prepared by SPRUCE

  • Required

  • Type: data_source

Complex Setup Parameters

Protein Name (flask_title): Prefix name used to identify the Protein. If not specified, it will use the title of the input protein.

  • Type: string

  • Default:

Maximum Number of MD Runs (max_md_runs): The maximum allowed number of MD runs

  • Type: integer

  • Default: 500

Number of MD Starts (n_md_starts): The number of MD starts for each ligand/conformer

  • Type: integer

  • Default: 1

Assign Ligand Partial Charges (charge_ligands): Assign ligand partial charges or not

  • Type: boolean

  • Default: True

  • Choices: [True, False]

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: 16

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

  • Type: integer

  • 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_2.0.0’, ‘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_2.0.0

  • Choices: [‘Gaff_1.81’, ‘Gaff_2.11’, ‘OpenFF_1.1.1’, ‘OpenFF_1.2.1’, ‘OpenFF_1.3.1’, ‘OpenFF_2.0.0’, ‘Smirnoff99Frosst’, ‘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 to speed up the MD

  • 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

  • Type: decimal

  • Default: 0.004