Antibody MD Simulations with Conformational Analysis

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

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

  • Solution-based/Biologics/Antibody Design/Target Preparation/Antibody MD Simulation

  • Task-based/Molecular Dynamics

Description

This floe performs MD simulations given one or more records with 3D antibodies. The system is solvated and each antibody design unit is treated in its entirety in a separate simulation.

Each input antibody 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) stage 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 is performed on the unrestrained flask.

Limitations: The input antibody structure needs to have reasonable 3D coordinates, all atoms enumerated, and correct chemistry defined (in particular, the bond orders and formal charges).

The starting configuration should not have very high gradients, and 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.

Potential Input Sources: Antibody Sequences to 3D Models Floe, Antibody Experimental Structure Prep Floe

Related Floes: Solvate and Run MD

Computational Cost Scaling: Larger systems and longer production run times are the biggest factors affecting computational costs.

Promoted Parameters

Title in user interface (promoted name)

MD Setup

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: 10.0

Trajectory Interval (prod_trajectory_interval): Trajectory saving interval in nanoseconds

  • Type: decimal

  • Default: 0.004

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’]

Solvation Parameters

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: 50.0