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Random Acceleration Molecular Dynamics in GROMACS

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Random Acceleration Molecular Dynamics (RAMD)

Background

Random Acceleration Molecular Dynamics (RAMD) is a method to carry out molecular dynamics simulations with an additional randomly oriented force applied to a molecule in the system.

Installation

See http://manual.gromacs.org/documentation/current/install-guide/index.html

HPC deployment with EasyBuild

The EasyBuild recipe is available here.

Usage

Please use following mdp options:

  • ramd

    RAMD will be applied.

  • ramd-seed

    Seed for random direction generator

  • ramd-eval-freq

    This parameter affect absolute dissociation time but have less effect on the relative dissociation times of different compounds. It is recommended to use default value.

  • ramd-force-out-freq

    This ramd parameter resets pull-nstxout and pull-nstfout.

  • ramd-ngroups

    The number of ramd groups defining the ligand-receptor pair. Below only the pull options for group 1 are given, further groups simply increase the group index number.

  • ramd-group1-force

    The force constant in kJ/mol/nm. Default value is 600 kJ/mol/nm. For a set of compounds with the dissociation rate expected to vary within the range of 0.1-0.0001 1/s, a random force magnitude of 600 kJ/mol/nm can be applied. If necessary, the force magnitude can be adjusted according to the longest and shortest dissociation time observed in simulations. The upper threshold of the force magnitude is determined by the fast-dissociated compounds, whose dissociation time should be longer than 100 ps. The lower threshold of the force magnitude depends on the computation facilities available.

  • ramd-group1-r-min-dist

    This parameter affect absolute dissociation time but have less effect on the relative dissociation times of different compounds. It is recommended to use default value.

  • ramd-group1-max-dist

    This value has to be adjusted for the system studied: no protein-ligand contacts should be observed in the last snapshot of a dissociation trajectory. Usually 4 nm is enough, but in the case of a long dissociation channel (as in many membrane proteins) maxDist must be increased accordingly. Method performance is not very sensitive to the upper limit of this parameter since motion of the free ligand due to the external force is very fast (i.e. the last part of the trajectory, where the ligand does not interact with the protein, usually has a negligible contribution to the observed dissociation time).

  • ramd-group1-receptor

    Receptor for the first RAMD group. Default name is 'Protein'.

  • ramd-group1-ligand

    Ligand for the first RAMD group. Default name is 'INH'.

  • ramd-group1-receptor-pbcatom

    The value will be forwarded to the associated pull group of the receptor. Default value is 0, which takes the middle atom (number wise).

  • ramd-group1-ligand-pbcatom

    The value will be forwarded to the associated pull group of the ligand. Default value is 0, which takes the middle atom (number wise).

  • ramd-pbc-ref-prev-step-com

    The value will be forwarded to pull-pbc-ref-prev-step-com. Default value is 'yes'.

  • ramd-connected-ligands

    If ‘yes’, the trajectory will be terminated when all ligands have left the radius. If one ligand leaves the radius, its last assigned force will continue to be applied until the simulation end or radius re-entry. If ‘no’, this should revert to standard RAMD for multiple disconnected ligands. Each ligand is subject to a RAMD force until the individual ligand has left the dissociation radius. The simulation stops when all ligands have left the dissociation radius. Default value is 'yes'.

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