Molecular Dynamics (MD) Integration
Execution and Performance
Q: How do I run MD simulations in ICM-Pro?
A: You have two primary options for running MD simulations:
- GUI: Run interactively within the ICM-Pro interface by navigating to MolMechanics > Molecular Dynamics.
- Command Line: Run in batch mode using the
runMDopenMM.icmscript located in the/bindirectory of your ICM distribution.
Q: How fast are MD simulations in ICM-Pro with GPU acceleration?
A: On a standard workstation GPU (such as those found in high-performance or gamer-class machines), ICM-Pro achieves simulation speeds of approximately 3–12 ps/s, or 0.2–1.0 μs/day.
Q: How is OpenMM integrated into ICM-Pro?
A: ICM-Pro provides a direct binary interface to OpenMM. This allows for:
- Seamless transfer of molecular objects to the MD engine.
- Automatic collection of trajectory snapshots directly into the ICM conformational stack for downstream analysis and visualization.
System Preparation and Parameters
Q: How does ICM-Pro help prepare a system for MD simulations?
A: ICM-Pro offers both scriptable and GUI-based workflows for automated system preparation. Key automated steps include:
- Solvation in a periodic water box.
- Assignment of AMBER atom types and charges.
- Generation of AM1-BCC charges for ligands.
- Initial energy minimization.
- Application of tethers or distance restraints.
- Implementation of the AMBER ff14SB force field for proteins.
- Support for building membrane systems.
Q: What integrator and time step are used in the MD simulations?
A: The simulations use a Verlet integrator with a default time step of 2 fs.
Q: What are the default force fields, and can alternative options like OpenFF be utilized?
A: By default, Amber ff14SB is used for proteins, and MMFF94 is used for ligands. The only alternative force field option currently supported is OpenFF (version 2.2.0).
Q: What periodic boundary condition (PBC) distances and electrostatic cutoffs are applied?
A: The system applies a smooth 10.0 Angstrom cutoff for non-bonded interactions alongside periodic boundary conditions.
Q: Which thermostats and barostats are employed during the simulation?
A: The simulations utilize an Andersen thermostat and a Monte Carlo barostat.
Q: What thermodynamic ensembles (e.g., NVE, NVT, NPT) are supported?
A: We exclusively employ the NPT (isothermal-isobaric) ensemble.
Q: Which minimization algorithm (e.g., steepest descent, conjugate gradient) is used?
A: Minimizations are handled independently within ICM and are performed outside of the core MD package.
Q: What type of simulation box is employed, and is it customizable?
A: The system utilizes a rectangular box only. While the box shape cannot be changed, custom box dimensions can be provided.
Q: Can I specify exact lipid counts (POPC/POPE) or manually edit the membrane composition (e.g., adding cholesterols or sphingolipids)?
A: Custom membrane composition is not supported at this time. We provide a pre-built membrane patch consisting of a fixed POPC/POPE mixture (45% POPC / 55% POPE).
Analysis and Validation
Q: What tools are available in ICM-Pro for analyzing MD trajectories?
A: Users can compute and visualize a wide range of structural and energetic metrics directly within the software, including:
- Interatomic distances.
- RMSD and RMSF.
- Contact areas and interaction types.
- Side-chain torsions (e.g., χ1 angles).
- RTCNN score drift over time.
- GB/SA binding free energy (ΔGbind).
- Radius of gyration.
- Physics-based scoring functions.
Q: Does ICM-Pro support batch MD simulations for hitlist validation?
A: Yes, batch MD simulations are fully supported to validate virtual screening hits. By utilizing the runMDopenMM.icm script, you can:
- Run MD relaxation on each docked complex.
- Collect multiple conformers per complex.
- Track RMSD and RTCNN score changes over time.