mdworks 0.5.0

Streamlines preparation and equilibration of molecular complex for MD simulations

Streamlines preparation and equilibration of molecular complex for MD simulations

Whether the atomic coordinates come from experimentally determined complex structures or from co-folding AI models, they often require adjustments such as correcting ligand stereochemistry or fixing other structural details needed for molecular dynamics. mdworks streamlines this process by making it easy to prepare a valid protein-ligand complex and setup up and run equilibrium MD simulations with OpenMM.

Install

Pixi

# Install pixi

$ curl -fsSL https://pixi.sh/install.sh | sh

Please check out Pixi installation for more details.

Mdworks

$ git clone https://github.com/sunghunbae/mdworks.git
$ cd mdworks
$ pixi install

Jupyter Notebook

1. Add mdworks environment to JupyterLab

python -m ipykernel install --user --name='mdworks'

2. Start the Jupyter lab

jupyter lab

Usage

from mdworks import ValidComplex
from mdworks.protocol import Equilibrium

vc = ValidComplex('protein_ligand_complex.cif')

# fix ligand stereochemistry
vc.fix_ligand(`target_SMILES`)

# am1bcc charges
vc.assign_ligand_charges()

# build openmm system
vc.build_system()

# run multi-stage equilibrium MD simulations
md = Equilibrium(vc)
md.run()

Multi-stage Equilibrium Protocol

Stage	temperature (K)	posres (kJ/mol/nm**2)	friction (1/ps)	time (ps)	timestep (fs)
Energy Minimization		1000
NVT cold	10	1000	5	100	1
NVT warm	10 -> 300	1000	1	145	2
NPT posres	300	1000 -> 0	1	300	2
NPT free	300	0	1	500	2
NPT production	300	0	1	user	2 or 4 (HMR)

Desmond-like Equilibrium Protocol

1. Energy Minimization
2. Brownian Dynamics NVT, T = 10 K, small timesteps, and restraints on solute heavy atoms, 100ps, k=50
3. NVT, T = 10 K, small timesteps, and restraints on solute heavy atoms, 12ps, k=50
4. NPT, T = 10 K, and restraints on solute heavy atoms, 12ps, k=50
5. NPT and restraints on solute heavy atoms, 12ps, k=50
6. NPT and no restraints, 24ps

Notes:

• 50 kcal/mol/A2 is equal to 20,920 kJ/mol/nm2 (1 kcal/mol/A2 = 418.4 kJ/mol/nm2)
• scale to the typically used positional restraint force constant (1000 kJ/mol/nm**2)

Stage	temperature (K)	posres (kJ/mol/nm**2)	friction (1/ps)	time (ps)	timestep (fs)
Energy Minimization		1000
Brownian	10	1000	50	100	1
NVT cold	10	1000	1	12	2
NPT cold	10	200	1	12	2
NPT warm	10 -> 300	40	1	12	2
NPT free	300	0	1	24	2
NPT production	300	0	1	user	2 or 4 (HMR)

Brownian MD

Brownian dynamics corresponds to:

• Motion dominated by friction + random force
• Inertia negligible
• Overdamped limit of Langevin dynamics
• Langevin dynamics with very high friction and small timestep
• Use with positional restraints is recommended
• When to use:
  • Initial solvent relaxation
  • Ion placement adjustment
  • Avoids solute distortion
  • Prevents pressure spikes later