Molecular Dynamics Simulation

Molecular Dynamics Simulation is an interface to minimization and molecular dynamics routines provided by MMTK, which is included with Chimera. Amber parameters are used for standard residues, and Amber's Antechamber module (also included with Chimera) is used to assign parameters to nonstandard residues.

Thanks to Victor Muñoz Robles and Jean-Didier Maréchal (The Computational Biotechnological Chemistry Team, Universitat Autònoma de Barcelona; funding from Ministerio de Ciencia e Innovación, Generalitat de Catalunya) for implementing this tool. See also: Minimize Structure, MD Movie, the Sophia plugin to Chimera

There are several ways to start Molecular Dynamics Simulation, a tool in the MD/Ensemble Analysis category.

Select model: The model of interest should be chosen by clicking to highlight its name in the list of models. All of the atoms for simulation should be included in this model; any other models will be ignored.

The dialog has four tabbed sections, in order of typical use:

• Prep Structure - structure cleanup and association with force field parameters
• Solvation - adding solvent and/or counterions to the system, setting box size for periodic boundary conditions
• Constraints Etc. - constraints and force field options
• Run Parameters - parameters for minimization, molecular dynamics (MD) equilibration, and MD production; initiating the calculations

← Prep Structure

Structure preparation is the same as for Minimize Structure and consists mainly of running Dock Prep to perform several tasks to prepare the system for energy calculations. These tasks may include calling AddH to add hydrogens and Add Charge to associate atoms with partial charges and other force field parameters. One of the following should be chosen before Dock Prep is started:

• Memorize options chosen in subsequent dialogs (default) - save the settings of Dock Prep and further tools it calls to prepare the structure; the settings are saved in the preferences file for future uses of Molecular Dynamics Simulation or Minimize Structure
• Use previously memorized options, if any - use settings saved with the preceding option in a prior use of Molecular Dynamics Simulation or Minimize Structure
• Neither memorize nor use memorized options - do not use previously saved settings; show the dialogs so that settings can be chosen explicitly for the current calculation, but do not save the settings

See the Minimize Structure documentation for details on force field parameters and associated limitations.

← Solvation

Buttons are provided to add solvent and counterions, if desired, by running the Solvate and Add Ions tools, respectively.

Periodic Boundary Conditions should only be used when a solvent box has been added. In that case, the “rgn size” reported by Solvate in the Reply Log can be entered as the dimensions of the (orthorhombic) periodic box. Alternatively, checking the Automatic box size option will use the bounding box of the chosen model along X, Y, and Z plus 2 Å padding on all sides. The automatic box size will be reported as the “universe size” in the Reply Log when the calculations are run.

← Constraints Etc.

• Fixed Atoms specifies whether to freeze some of the atoms in place during the calculations. Atoms to freeze in place are indicated by selection, either those selected or unselected when the Set button is clicked. However, all atoms in the chosen model will be included in the energy calculations, regardless of whether they are held fixed. (Only the minimize command with fragment true allows excluding some of the atoms in a model from energy calculations.)
• Translation remover: start [i] end [j] apply every [N] steps - whether to subtract out global translational motion during MD, and if so, at which steps; default the first, third, fifth, etc. through the end (the end value j can be left blank)
• Rotation remover: start [i] end [j] apply every [N] steps - whether to subtract out global rotational motion during MD, and if so, at which steps; default the first, third, fifth, etc. through the end (the end value j can be left blank)

** If periodic boundary conditions are used, no distance cutoff d should exceed half of the smallest box dimension. **

Electrostatic interaction method:

• default - MMTK default; in MMTK 2.7.9, Ewald (see below) if periodic boundary conditions are used, otherwise direct
• direct - no cutoff; all pairs, subject to the minimum image convention if periodic boundary conditions are used
• cutoff [d] Å - pairs within the distance cutoff, plus a charge-neutralizing surface charge density around the cutoff sphere
• Ewald - Ewald summation, applies only when periodic boundary conditions are used
• screened [d] Å beta [β] - the real-space part of the Ewald sum (no reciprocal sum) with a charge-neutralizing surface charge density around the cutoff sphere; requires input of the real-space cutoff distance d and the Ewald screening parameter β. The cutoff distance d should be significantly larger than 1/β.

Lennard-Jones interaction method:

• default - MMTK default; in MMTK 2.7.9, direct (see below)
• direct - no cutoff; all pairs, subject to the minimum image convention if periodic boundary conditions are used
• cutoff [d] Å - pairs within the distance cutoff

← Run Parameters

Settings are shown separately for the four subsections:

• minimization
• equilibration
• production
• other runtime options

← Minimization

• Minimize before MD - whether to include minimization in a run

  Steepest descent minimization is performed first to relieve highly unfavorable clashes, followed by conjugate gradient minimization, which is much slower but more effective at reaching an energy minimum after severe clashes have been relieved. Energies (kJ/mol) are reported in the Reply Log. **Step numbers reported by MMTK are 2 greater than the actual numbers of minimization steps performed. The additional “steps” are not minimization steps but operations required to obtain gradient values and updated coordinates.**

• Steepest descent steps (default 100) - number of steps of steepest descent minimization to perform before any conjugate gradient minimization
• Steepest descent step size (Å) (default 0.02) - initial step length for steepest descent minimization
• Conjugate gradient steps (default 10) - number of steps of conjugate gradient minimization to perform after finishing any steepest descent minimization
• Conjugate gradient step size (Å) (default 0.02) - initial step length for conjugate gradient minimization

← Equilibration

• Equilibrate [N] steps - whether to include equilibration MD in a run, and if so, how many steps (default 5000)
  
  
• Temperature control method:
  • Heater (default) - rescale velocities to increase temperature gradually
    • temp1 (K) [T1] temp2 (K) [T2] gradient (K/ps) [g] - set heater initial and target temperatures (default 0 and 298 K, respectively) and gradient (default 10 K/ps)
    • start [i] end [j] apply every [N] steps - at which steps to apply the heater: default the first, third, fifth, etc. through the end (the end value j can be left blank)
  • Velocity scaler - rescale velocities to attain a target temperature; usually done during initial equilibration
    • temp (K) [T] allowed deviation [w] - set target temperature (default 298 K) and allowed deviation in either direction before rescaling takes place (default 0 K)
    • start [i] end [j] apply every [N] steps - at which steps to rescale velocities: default the first, third, fifth, etc. through the end (the end value j can be left blank)
• Barostat reset: start [i] end [j] apply every [N] steps - whether to reset the barostat coordinate to zero (for initial equilibration of systems in the NPT ensemble), and if so, at which steps: default the first, third, fifth, etc. through the end (the end value j can be left blank)
• Time step (fs) (default 1)
• Output trajectory file - output trajectory file; frequency of saving is set in the other runtime options
• Output restart-trajectory file - output restart file, needed as input to the production phase; frequency of saving is set in the other runtime options

← Production

• Include production phase [N] steps - whether to include production MD in a run, and if so, how many steps (default 5000)
  
  
• Input restart-trajectory file (from previous equilibration or production) - restart file from previous MD (required), automatically kept the same as the restart file specified at the bottom of the equilibration section
• Andersen barostat: pressure (bars) [P] relaxation time [τ_P] - whether to keep pressure constant, and if so, the target pressure (default 1.0132 bars = 1 atm) and relaxation time (default 1.5 ps)
• Nosé thermostat: temperature (K) [T] relaxation time [τ_T] - whether to keep temperature constant, and if so, the target temperature (default 298 K) and relaxation time (default 0.2 ps)
• Time step (fs) (default 1)
• Output trajectory file - output trajectory file; frequency of saving is set in the other runtime options
• Output restart-trajectory file - output restart file; optional, but required as input for any subsequent MD runs starting from the end of this production run; frequency of saving is set in the other runtime options

← Other Runtime Options

• Use multiple CPUs - whether to use multiple CPUs (if available)
• Save once every [N] steps - how often to write to trajectory output files (default every 10 steps)
• “Live” trajectory - whether to update the structure in Chimera as the calculation progresses