**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

This tool was developed for teaching about molecular dynamics using simulations on small molecules. Compared to dedicated packages for molecular simulation (Amber, Gromacs, others), the calculations are relatively slow and parameter options few. Although it may be useful for limited sampling and relaxation of macromolecular structures and complexes, this tool is not suitable for long simulations on macromolecules, such as needed to predict changes in stability or binding energy. For such applications, other packages should be used instead. |

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 [*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

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 [*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**

**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) [*P*] relaxation time [*τ*] - whether to keep pressure constant, and if so, the target pressure (default_{P}**1.0132**bars = 1 atm) and relaxation time (default**1.5**ps)**Nosé thermostat**: temperature (K) [*T*] relaxation time [*τ*] - whether to keep temperature constant, and if so, the target temperature (default_{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 / May 2020