Desmond

Usage

from mdscribe.desmond import Multisim

# read template .msj and .cfg
md_msj = Multisim(template="desmond-md.msj")
md_cfg = Multisim(template="desmond-md.cfg")

with open(msj_file,"w") as msj:
    # modify desmond msj template
    md_msj.dot.simulate[-1].cfg_file = cfg_file_basename

    # Setting up restraints using the restraints keyword:
    # https://www.schrodinger.com/kb/332119
    if args.posres_force > 0.0:
        # print the restraints in the multisim log file
        md_msj.dot.simulate[-1].print_restraint = 'true'

        # add the new terms defined in "restraints.new" to existing restraints.
        # The default is restraints.existing = ignore which will 
        # delete existing terms before adding any new ones.
        # md_msj.dot.simulate[-1].restraints.existing = 'retain'

        md_msj.dot.simulate[-1].restraints.new = [
            {
                'name'              : 'posre_harm',
                'atoms'             : [ f'"{args.posres}"' ],
                'force_constants'   : [ args.posres_force, ] * 3,
            }
            ]
        # force constants in the x, y, and z direction

    # write to a .msj file
    md_msj.write(msj)

with open(cfg_file,"w") as cfg:
    # modify desmond cfg template
    md_cfg.dot.randomize_velocity.seed = random.randint(1000, 9999)
    md_cfg.dot.time = total_simulation_time
    md_cfg.dot.temperature = t_schedule
    md_cfg.dot.trajectory.interval = args.interval

    # write to a .cfg file
    md_cfg.write(cfg)

Metadynamics

Collective variable types

type	Description	Default Width	Wall	Floor	Atom sites
dist	Distance	0.05 Å	yes	yes	2
angle	Angle	2.5°	yes	yes	3
dihedral	Dihedral	5.0°	no	no	4
rgyr	Radius of gyration	0.1 Å	no	no	1
rgyr_mass	Mass-weighted radius of gyration	0.1 Å	no	no	1
rmsd	RMSD from aligned starting structure	0.1 Å	no	no	1
rmsd_symm	Symmetry aware RMSD	0.1 Å	no	no	1
zdist	Distance along the z axis	0.05 Å	yes	yes	1
zdist0	Absolute distance along the z axis	0.1 Å	yes	yes	1
whim1	WHIM1 - first principal moment [35]	0.5 Å2	no	no	1
whim2	WHIM2 - second principal moment [35]	0.25 Å2	no	no	1

Choice of the bias factor (kTemp)

In well-tempered metadynamics, the height of the deployed Gaussians are rescaled (decreased) during simulation time by: omega_0 * exp(-V/(kB * ΔT)) Where omega_0 is the initial hill height, V is the bias potential and the denominator in the exponential, kB * ΔT,
is the bias factor (kTemp). During well-tempered metadynamics, the dynamics of the system are effectively accelerated (without heating up the system) up to T + ΔT, where T is the chosen MD simulation temperature. The choice of the bias factor value is guided by the highest barrier in the simulation system which the well-tempered metadynamics run should overcome. Here are some suggestions, assuming that the initial hill height ω0 (height parameter in the Metadynamics panel) has been set to 0.3 kcal/mol:

Max. barrier height (kcal/mol)	kTemp (kcal/mol)
3	1.7
6	3.4
10	5.6
15	8.4
20	11.2

Examples

distance:
    cv = [
        {atom = ["res. UNK" "res. 849" ]
        type = dist
        wall = 40
        floor = 10
        width = 0.05
        }
    ]

dihedral:
    cv = [
        {atom = [404 406 407 415 ]
        type = dihedral
        width = 5.0
        }
        {atom = [406 407 415 417 ]
        type = dihedral
        width = 5.0
        }
    ]

zdist(membrane):
    cv = [
        {atom = ["res. UNK"]
        type = zdist
        width = 0.05
        wall = 20
        floor = 5
        }
        ]

rmsd:
    cv = [
        {atom = ["res. UNK" "res. 849" ]
        type = rmsd
        width = 0.1
        }
    ]

Extending Simulations

See https://www.schrodinger.com/kb/788642 for extending metadynamics simulation.

Command-Line Interface (CLI)

desmond.Multisim class are used to build below CLI.

Command-line interface	Description
`mdinfo`	Display a running Desmond MD simulation information in the Amber-style
`batch-desmond-setup`	Setup/parametrize Desmond MD simulations
`batch-desmond-min`	Run Desmond energy minimizations
`batch-desmond-md`	Run Desmond MD simulations
`batch-desmond-metad`	Run metadynamics MD simulations
`batch-desmond-pli`	Analyze protein-ligand interactions
`batch-desmond-extend`	Extend Desmond MD simulations
`batch-desmond-report`	Generate reports for Desmond MD simulations
`batch-desmond-dihedral`	Analyze dihedral angles from Desmond MD trajectories
`batch-desmond-ligrmsd`	Analyze ligand rmsd from Desmond MD trajectories
`batch-desmond-rg`	Analyze radius of gyration from Desmond MD trajectories

For more helps, $ command --help.

`mdscribe.desmond.cli`

`SCHRODINGER = os.environ['SCHRODINGER']` `module-attribute`

`USER = os.environ['USER']` `module-attribute`

`multisim = '{}/utilities/multisim'.format(SCHRODINGER)` `module-attribute`