ACEMD Manual¶

Introduction¶

ACEMD is a high performance molecular dynamics code for biomolecular systems designed specifically for NVIDIA GPUs. Simple and fast, ACEMD uses very similar commands and input files of NAMD and output files as NAMD or Gromacs. The three design target features of ACEMD are:

ACEMD is fast, as it was designed from scratch to be an optimized MD engine that exploits the computational power of graphical processing units (GPUs). ACEMD provides the equivalent performance of parallel CPU simulations using many tens to hundreds of processors, depending on the number and type of GPU cards installed. ACEMD has the following features and capabilities:

• Force fields Amber, CHARMM, OPLS and Martini
• Input file formats PDB, PSF, PRMTOP, NAMD Bincoor
• Output file formats PDB, NAMD Bincoor, DCD, XTC
• Electrostatics PME, integrator Velocity Verlet, long timesteps with H mass repartitioning, unit cell cuboid, fully periodic
• Thermostat Langevin, barostat Berendsen
• Constraints and restraints M-SHAKE with RATTLE correction, positional harmonic restraints
• Scripting TCL and C interfaces
• Metadynamics using PLUMED 1.3/2.0, including parallel tempering metadynamics and replica exchange
• Total integration with HTMD

Fundamental units¶

• Length Ångström (0.1nm)
• Energy kcal/mol
• Temperature Kelvin
• Mass g/mol

These yield the derived units:

• time unit t = 48.88821 femtoseconds$• velocity unit v = Ångström/t • Boltzmann constant kB = 0.001987191 kcal/mol/K Force field parameters¶ The default force-field formats used by ACEMD are CHARMM including cross-term support and Amber force-fields. The code can also simulate OPLS force-fields in CHARMM format via translated force-fields. To build the molecular system it is possible to use HTMD. CHARMM force field¶ ACEMD reads directly the psf and parameter files for Charmm. The topology and parameters force fields for CHARMM are included in the HTMD distribution. Also the quality of the forcefields have greatly improved in the last years. HTMD always provide the latest version. • CHARMM36 - this is the latest available forcefield for Charmm (Feb2016). It is probably the best forcefield for membrane proteins. The free (for academics) online website CHARMM-GUI is very good to set up a membrane system also changing the type of lipids. However it is still possible to the same using VMD, just a bit more scripting is required. • CHARMM22star - this is a revised version of the Charmm forcefield derived by DE SHAW research. It is older than Charmm36 but it works better for protein folding. You can also mix Charmm22star for protein with Charmm36 for proteins. Note that this is different from Charmm22 without star which should never be used. Charmm27 also widely used is known to overstabilize helices and should also be avoided now. AMBER force field¶ AMBER input files are read by ACEMD, so it is only necessary to provide a PDB instead of the CRD file (use HTMD to convert). The following commands in your ACEMD configuration files but they are automatically set by HTMD if you prepared the system with it: coordinates your_pdb_file amber on parmfile your_topology_file 1-4scaling 0.83333  We suggest that you keep switching when using AMBER force fields in ACEMD to avoid force discontinuities at the cutoff distance as you do for CHARMM. The latest forcefield from Amber is the best to use. OPLS force field¶ The use of OPLS force field parameters is possible using the version in CHARMM format, but only for the protein portion. This requires the use of the configuration parameter “vdwgeometricsigma on”. This forcefield is less used and so less tested, in particular we have not tested the porting Running ACEMD¶ ACEMD is a command line program, invoked with the command ACEMD. If ACEMD is not found, or reports any other error at startup, please refer to the ACEMD Installation Guide. Specifying an Input File¶ When run without any arguments ACEMD will attempt to read a configuration from the file input and run a simulation on the first GPU in the system. If the input file does not exist ACEMD will print out a help message and exit. An alternative input file can be specified by putting the filename on the command line, for example: $ acemd equilibrate.conf


The input file contains all of the commands required to configure and run a simulation. The specification for the system to be simulated resides in separate files, eeg PDB, Bincoor files for coordinates, PSF, PRMTOP files for topology and force field parameters.

Command Help¶

ACEMD contains a built-in reference manaual for all configuration commands, which can be access from the command line and online at ACEMD command reference. To all commands that pertain to a particular topic, use the command:

$acemd --command [section]  where section is one of the topics listed by the command acemd -command alone. For help on a particular command, use: $ acemd --command [command]


This will give a description of the command’s function along with any required arguments and default value. For example:

$acemd --command langevintemp langevintemp <+ve float> [0.] The set point in K for the Langevin thermostat  Selecting a GPU¶ ACEMD Basic will run only on the first GPU in the system. The following section applies only to ACEMD Pro users. ACEMD will by default try to run on the first GPU available in the system. If several instance of ACEMD are launched they will normally1 all run on the first GPU, leaving any other devices idle. To explicity set the GPU to run on, use the command-line flag -device: $ acemd --device 2


If the device specified does not exist, ACEMD will automatically select an available GPU. If several GPUs are given as a comma-separated list to -device, ACEMD will attempt to run a single simulation in parallel accross them. For example:

$acemd --device 0,1,2  When running in parallel note that performance may not always improve as more GPUs are added. Running parallel ensembles¶ ACEMD Pro supports ensemble simulations for replica exchange molecular dynamics. Ensemble mode is automatically enabled if ACEMD is run via MPI. For example, to run an 8 replica ensemble: $ mpirun -np 8 acemd input


Note that this assumes that the MPI environment is appropriately configured. In this mode no explicit -device flag should be used. ACEMD will run one replica per GPU and assume that all GPUs on the allocated hosts are available for its use.

Simulation Configuration¶

ACEMD simulations are configured using a single input file. This file is parsed as a TCL script, so can include programmatic elements. The syntax of the input script is very similar to that of NAMD. The script is read in its entirety before the simulation commences. If commands are duplicated, generally only the last setting will be used. For example:

structure struct1.pdb
structure struct2.pdb
run 100
run 1000


configures ACEMD to use the structure file struct2.pdb and to run for 1000 iterations.

Quick Configurations¶

A complete specification for an ACEMD simulation requires configuration of input and output files, force field parameters and thermodynamic ensemble. Explicitly writing the full configuration can result in a long input file. ACEMD includes a set of pre-defined parameter sets for common simulation configurations. These are activated using the protocol command. For example:

protocol run/NVT
protocol ff/Amber


configures ACEMD to simulate in the isothermal ensemble and to expect Amber force field input files. Unlike most other commands, protocol is executed as soon as it is encountered and can be specified multiple times.

If ACEMD is run with the flag -verbose then as each protocol is executed, the commands that it specifies are printed out in the log file. These can be captured for use in an explicit input file. Any inappropriate settings can be overriden by re-issuing the command afterwards. For example:

protocol run/NVT
protocol ff/Amber
parmfile amber.prmtop
run      10ns


changes the default setting for the name of the Amber parameter file and the length of the simulation. The following protocols are available:

• Run types
• run/NVT run in the isotermal ensemble, using a Langevin thermostat set at 300 K
• run/NPT run in the isothermal-isobaric ensemble, using a Langevin thermostat at 300.K and a Berendsen barostat at 1atm.
• run/NVE run in the microcanonical ensemble.
• run/CG run a coarse-grained simulation.
• Force field types
• ff/Amber configure for Amber force fields
• ff/CHARMM27 configure for CHARMM version 22 and 27 force fields
• ff/CHARMM36 configure for CHARMM version 36 force fields
• ff/Martini configure for Martini force field
• ff/OPLS configure for OPLS force field

These protocols assume the following file naming conventions which however you can override:

• Coordinates: structure.pdb
• CHARMM Topology: structure.psf
• CHARMM Parameters: parameters
• Amber Parameters: structure.prmtop
• Extended System: input.xsc
• Trajectory: trajectory.xtc
• Final state: output.coor output.vel output.xsc

NVT vs NPT ensemble¶

The Langevin thermostat is needed to keep the system in the NVT ensemble. This is the suggested ensemble for production runs. The langevindamping should be as small as possible in order to thermalize the system without affecting the transport parameters (diffusion). We suggest to use langevindamping 0.1 for all production runs in NVT. A langevindamping 1 is better during equilibration.

ACEMD implements a Berendsen barostat designed for the equilibration of molecular systems (globular and in a membrane) to then start NVT production runs. With the system sizes which are achievable nowadays it is not necessary to have a pressure control in the production run, unless you really know what you are doing (for large number of atoms all ensembles are equivalent statistically). For molecular systems up to 100,000 atoms in a membrane allow for an equilibration of 20 ns, for globular proteins 1 to 5 ns are sufficient.

Input Files¶

ACEMD expects input coordinates in PDB or Bincoor format, specified using the commands coordinates and bincoordinates respectively. An initial velocity field may also be supplied using velocities or binvelocities. The dimensions of the unit cell may also be specified in a file given by extendedsystem. If present, this will over-ride any celldimensions setting.

For simulations using CHARMM format models, a topolgy file in PSF format must be specified with structure along with force field parameters by parameters. For Amber simulations, the combined topology/force field PRMTOP file is required, specified with the command parmfile.

Output Files¶

ACEMD can produce trajectories in both DCD and XTC formats. XTC trajectories are compressed, so save on disk space, but may not be read by all analysis programs.

At the end of a simulation, ACEMD also outputs the final system state (coordinates and velocities) in NAMD Bincoord format. The filename prefix of these files is by defualt output and can be overriden with the command outputname.

If the barostat is enabled, the unit cell dimensions are emitted into the output file suffix .xstfile whenever the energies are printed.

Standard output¶

During a run ACEMD will print a summary of the system energies to stdout. This should sually be saved in a log file for future reference using re-direction, for example:

$acemd --device 1 input > log.txt  During ensemble runs ech replica’s log file is automatically redirected to a file called log.N, where N is the 0-based replica index. All log lines not containing an energy are prefixed with # to facilitate greping. Attention should be paid to the log for lines prefixed # WARNING. These will generally indicate when a default value for a parameter has been used, indicating that a configuration option may have been unintentionally omitted. The log also contains a measure of the current performance of the simulation, expressed in ns/day, along with an estimate of the completion time. GPU temperatures and fan speeds are also printed, for monitoring purposes. An example is shown below: # Step Bond Angle Dihed Elec VDW PE KE External Total Temp Pres PresAve 0 74.8328 340.6115 750.4010 -72143.0851 4123.4423 -66853.7976 14371.4091 0.0000 -52482.3885 298.9427 16519.2258 16519.2258 100 486.7075 1343.1273 1024.4554 -78224.9388 6361.2833 -69009.3652 15448.9447 0.0000 -53560.4206 321.3568 -35.9722 -250.7526 # Simulation rate 19.32 (ave) 19.32 (inst) ns/day. Estimated completion Wed Aug 28 15:53:34 2013 # NVML : 0 : Fan 31% Temp 43C Mem Used 253MB Free 769MB Total 1023MB  Restarting¶ ACEMD can perform checkpointing to allow an aborted simulation to be resumed, using the commands restart, restartname and restartfreq. Frequency of restart dump should generally be set to match the trajectory output frequency. Checkpointing and restarting is very powerful in ACEMD and seamless. Trajectory files are automatically appended upon a restart. Restart coordinate and velocity files are in NAMD Bincoord format. Simulations started using protocols will be configured to restart by default. Advanced material¶ Tcl Scripting¶ The entire input file is seen by ACEMD as a Tcl script. You can interleave Tcl command with the commands shown in the command reference manual. Tcl is also useful to manipulate the molecular systems by reading coordinates, velocities and forces on-the-fly while the simulation is running. Tcl scripts are executed in the CPU, so they can be expensive if the number of atoms involved is large (depending on system size, but target for less than 100 atoms if possible). For simple harmonic positional constraints use the constraints command instead. ACEMD calls two tcl functions, calc_forces_init at startup and calc_forces at every step. Note that calc_forces is processed on the CPU. Harmonic positional constraints can be applied on selected atoms. This is useful during equilibration but also in production runs, so ACEMD implements it in the fastest possible way: directly computed on the GPU. There are no limitations on the number of atoms to which the constraints are applied. Similar and more flexible constraints can also be applied using Tcl scripting. For instance the following Tcl scripting example applies a flat bottom potential restrain to a single atom group in 1D #Normal acemd conf file protocol run/NVT protocol ff/Amber run 1000 # TCL set structure mystructure.pdb set Krestrain 10 set axis {1 0 0} set logfreq 1000 tclforces on # proc restrain1_1D_flatbottom { _coor O group Dir K d log } { # USAGE: restrains 1 group of atoms with a flat bottom potential # at a distance$d from $O in the direction$Dir with constant $K upvar$_coor coor
global logfreq
#
set dr [expr [vecdot $coor($group) $Dir] - [vecdot$O $Dir] ] set DR [expr abs($dr) - $d] if {$DR > 0} {
if {$dr > 0} { set DR [expr$dr - $d] } else { set DR [expr$dr + $d] } set f [vecscale [expr -$K*$DR]$Dir]
addforce $group$f
set step [ getstep ]
if {$step %$logfreq == 0} {
set E [ expr 0.5*$K*$DR*$DR ] print "$log $step$dr $DR$E"
}
}
}
#
proc calcforces_init {} {
global structure coor1 glist1 gcom1
#
# Extraction of atoms and coordinates from pdb file.
readpdb pdb $structure # # Loading of atoms with beta column equal to '1' and storage of # selected atoms index values and coordinates. loadsystem pdb 1 id1 coor1 # # Creation of group corresponding to the center of mass of # selected atoms to which we will apply the restrain. set gcom1 [ addgroup$id1 ]
#
# Creation of a list of groups for every selected atom.
# We need this to obtain later the reference position for the center of mass.
get_groups id1 glist1
#
}
#
proc calcforces {} {
global coor1 glist1 gcom1 axis Krestrain logfreq
#
#
## Getting atom selection coordinates
# Current
set gcom1_pos $coords($gcom1)
# Reference
set gcom1_start [ center_of_mass glist1 coor1 ]
#
## Applying a 1D restrain to the center of mass of the atom selection
## using as reference coordinates those extracted from the pdb.
restrain1_1D_flatbottom $gcom1_start$gcom1 $axis$Krestrain 0 "log_text"
#
return;
}


Debug TCL scripts¶

The following definitions can be prepended before the TCL script in order to enable light debugging (function calls).

rename proc _proc
_proc proc {name arglist body} {
_proc $name$arglist [concat "proc_start;" $body ";proc_end"] } _proc proc_start {} { puts stderr ">>> ENTER PROC [lindex [info level -1] 0]" for {set level [expr [info level] -1]} {$level > 0} {incr level -1} {
puts stderr "  LEVEL $level: [info level$level]"
}
puts stderr ""
}
_proc proc_end {} {
puts stderr ">>> LEAVE PROC [lindex [info level -1] 0]\n"
}


The following functions can be added after the calcforces definition to enable very verbose (complete trace) debugging.

proc tracer { a b } { puts "TRACE $b:$a" }
trace add execution calcforces enterstep tracer


PLUMED library¶

Interfaces exist for PLUMED (versions 1 and 2), a flexible library implementing a number of biased free energy calculation methods, such as metadynamics. Please see the ACEMD-PLUMED repository for examples.

Plugin interface¶

ACEMD is easily extended by adding plugin modules written in C and dynamically loaded at simulation time. The plugin interface give access to the position, velocities and forces at each iteration from a C interface. It is easy to think of ways on which users might want to customize ACEMD for their needs.

Getting support¶

Users can receive individual and confidential support at Acellera Ltd via support@acellera.com.

Citations¶

When publishing results with ACEMD please cite:

• M. Harvey, G. Giupponi and G. De Fabritiis, ACEMD: Accelerated molecular dynamics simulations in the microseconds timescale, J. Chem. Theory and Comput. 5, 1632 (2009).

Additionally, please read and consider citing the following methods papers:

• M. J. Harvey and G. De Fabritiis, An implementation of the smooth particle-mesh Ewald (PME) method on GPU hardware, J. Chem. Theory Comput., 5, 2371–2377 (2009)
• U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee and L. G. Pedersen, A smooth Particle Mesh Ewald Method, J. Chem. Phys. 103, 8577 (1995)
• Mass repatitioning (dt=4fs) Feenstra, K. A., Hess, B., Berendsen, H. J. C., Improving efficiency of large time-scale molecular dynamics simulations of hydrogen-rich systems, J. Comp. Chem. 20, 786(1999).
• M-SHAKE V. Krautler, W. F. Van Gunsteren, P. H. Hunenberger, A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations, J. Comp. Chem. 22, 501 (2001).
• RATTLE H. C. Andersen, Rattle: A velocity version of the shake algorithm for molecular dynamics calculations, J. Comp. Phys. 52, 24 (1983).