Bound Protein-Ligand 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 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
Analyze Protein-Ligand 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 to 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)
Inputs
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
Outputs
MD Output Dataset (eq_out): Output dataset of bound/unbound 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 Bound Protein-Ligand MD
Bound and Unbound Production Parameters
Number of Bound State MD Starts (n_md_starts): The number of Bound MD starts for each ligand/conformer
Type: integer
Default: 1
NPT Production Runtime (prod_bn_ns): NPT simulation production time in nanoseconds
Type: decimal
Default: 2.0
Complex Setup Parameters
Protein Name (flask_title): Prefix name used to identity the Protein. If not specified, it will use the title of the input protein.
Type: string
Default:
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 Å2)
Type: decimal
Default: 0.1
Assign Ligand Partial Charges (charge_ligands): Assign Ligand Partial Charges or not
Type: boolean
Default: True
Choices: [True, False]
Equilibration 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]
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