**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**

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

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.

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.

**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 [**- whether to subtract out global translational motion during MD, and if so, at which steps; default the first, third, fifth,*i*] end [*j*] apply every [*N*] steps*etc.*through the end (the end value*j*can be left blank)**Rotation remover: start [**- whether to subtract out global rotational motion during MD, and if so, at which steps; default the first, third, fifth,*i*] end [*j*] apply every [*N*] steps*etc.*through the end (the end value*j*can be left blank)

** If periodic boundary conditions are used, no distance cutoff

dshould 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, otherwisedirectdirect- no cutoff; all pairs, subject to the minimum image convention if periodic boundary conditions are usedcutoff [- pairs within the distance cutoff, plus a charge-neutralizing surface charge density around the cutoff sphered] ÅEwald- Ewald summation, applies only when periodic boundary conditions are usedscreened [- 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 distanced] Å beta [β]dand the Ewald screening parameterβ. The cutoff distancedshould 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 usedcutoff [- pairs within the distance cutoffd] Å

**Settings** are shown separately for the four subsections:

**Minimize before MD**- whether to include minimization in a runminimization is performed first to relieve highly unfavorable clashes, followed by*Steepest descent*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*conjugate gradient***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

**Equilibrate [**- whether to include equilibration MD in a run, and if so, how many steps (default*N*] steps**5000**)

**Temperature control method**:**Heater**(default) - rescale velocities to increase temperature gradually**temp1 (K) [**- set heater initial and target temperatures (default*T1*] temp2 (K) [*T2*] gradient (K/ps) [*g*]**0**and**298**K, respectively) and gradient (default**10**K/ps)**start [**- at which steps to apply the heater: default the first, third, fifth,*i*] end [*j*] apply every [*N*] steps*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) [**- set target temperature (default*T*] allowed deviation [*w*]**298**K) and allowed deviation in either direction before rescaling takes place (default**0**K)**start [**- at which steps to rescale velocities: default the first, third, fifth,*i*] end [*j*] apply every [*N*] steps*etc.*through the end (the end value*j*can be left blank)

**Barostat reset: start [**- 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,*i*] end [*j*] apply every [*N*] steps*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**

**Include production phase [**- whether to include production MD in a run, and if so, how many steps (default*N*] steps**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) [**- whether to keep pressure constant, and if so, the target pressure (default*P*] relaxation time [*τ*]_{P}**1.0132**bars = 1 atm) and relaxation time (default**1.5**ps)**Nosé thermostat: temperature (K) [**- whether to keep temperature constant, and if so, the target temperature (default*T*] relaxation time [*τ*]_{T}**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**

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

UCSF Computer Graphics Laboratory / February 2017