Next: Examples of input files
Up: Alchemical Free Energy Methods1
Previous: Theoretical Background
Contents
Index
Implementation of the free energy methods in NAMD
The procedures implemented in NAMD are particularly
adapted for performing free
energy calculations that split the
reaction path into a number of non-physical,
intermediate states, or ``windows''. Separate simulations
can be started for each window.
Alternatively, the TCL scripting ability of
NAMD can be employed advantageously
to perform the complete simulation in a single run.
An example, making use of such a script, is supplied at the end
of this section.
The following keywords can be used to run alchemical free
energy calculations, whether FEP or TI. Each keyword has two variants: one that is used in FEP calculations and a second that should be used when performing TI. The FEP and TI variants are seperated by slashes like so: fepKeyword / tiKeyword, listing first the FEP keyword and second the TI keyword. The FEP and TI specific keywords should be used exclusively with FEP or TI, respectively, and should not be intermixed during a simulation.
- fep / thermInt
Is an alchemical free energy perturbation to be performed?
Acceptable Values: on or off
Default Value: off
Description: Turns on alchemical transformation methods in NAMD.
- lambda / tilambda
Current value of the coupling parameter
Acceptable Values: positive
decimal between 0.0 and 1.0
Description: The coupling parameter value determining the
progress of the perturbation for FEP or TI.
- lambda2 / Not applicable
Forward projected value of the coupling
parameter
Acceptable Values: positive decimal between 0.0 and 1.0
Description: The lambda2 value corresponds to the coupling parameter to be used for
sampling in the next window. The free energy difference between lambda2 and lambda is calculated. Through simulations
at progressive values of lambda and lambda2 the
total free energy difference may be determined.
- fepEquilSteps / tiEquilSteps
Number of equilibration steps in a window,
prior to data collection
Acceptable Values: positive integer less than numSteps or run
Default Value: 0
Description: In each window fepEquilSteps/tiEquilSteps steps of equilibration can be
performed before ensemble averaging is initiated. The output also contains
the data gathered during equilibration and is meant for analysis of
convergence properties of the alchemical free energy calculation.
- fepFile / tiFile
pdb file with perturbation flags
Acceptable Values: filename
Default Value: coordinates
Description: pdb file to be used for indicating the status of all
atoms pertaining to the system, with respect to the alchemical transformation.
If this parameter is not declared specifically, then the
pdb file specified by
coordinates is utilized for this information.
- fepCol / tiCol
Column in the fepFile/tiFile that carries
the perturbation flag
Acceptable Values: X, Y, Z, O or B
Default Value: B
Description: Column of the pdb file to use for retrieving the status
of each atom, i.e. a flag that indicates which atom will be perturbed
in the course of the alchemical transformation.
A value of -1 in the specified column indicates that the atom will
vanish as
moves from 0 to 1, whereas a value of 1
indicates that it will grow.
- fepOutFreq / tiOutFreq
Frequency of free energy output in time-steps
Acceptable Values: positive integer
Default Value: 5
Description: Every fepOutFreq/tiOutFreq number of MD steps, the output file
fepOutFile/tiOutFile is updated by dumping energies that are
used for ensemble averaging.
This variable could be set to 1 to include all the
configurations for ensemble averaging. Yet, it is recommended
to update fepOutFile/tiOutFile energies at longer intervals
to avoid large files containing highly correlated data, unless a post-treatment,
e.g. Bennett's acceptance ratio (BAR) [3] or simple overlap
sampling (SOS) [32], is to be performed.
- fepOutFile / tiOutFile
Alchemical free energy output filename
Acceptable Values: filename
Default Value: outfilename
Description: An output file named fepOutFile,
containing the FEP energies, or tiOutFile, containing the TI derivatives, dumped every fepOutFreq/tiOutFreq steps.
- fepVdwShiftCoeff / tiVdwShiftCoeff
Soft-core van der Waals radius-shifting coefficient
Acceptable Values: positive decimal
Default Value: 5
Description: This is a radius-shifting coefficient of
that is used
to construct the modified vdW interactions during alchemical free energy calculations.
Providing a positive value for fepVdWShiftCoeff/tiVdwShiftCoeff ensures that the vdW potential
is finite everywhere for small values of
, which significantly improves the
accuracy and convergence of FEP and TI calculations, and also prevents overlapping particles
from making the simulation unstable. During FEP and TI, assuming
denotes an absence of interaction, the interatomic distances used in
the Lennard-Jones potential are shifted according to [5,33]:
- fepElecLambdaStart / tiElecLambdaStart
Value of
to introduce electrostatic interactions
Acceptable Values: positive decimal
Default Value: 0.5
Description: In order to avoid the so-called ``end-point catastrophes'', it is crucial to
avoid situations where growing particles overlap with existing particles with
an unbounded interaction potential, which would approach infinity as the
interaction distance approaches zero [5,13]. One possible route for
avoiding overlap of unbounded electrostatic potentials consists of allowing a
bounded (soft-core) vdW potential, using a positive value of fepVdWShiftCoeff/tiVdwShiftCoeff, to repel first all overlapping particles at low values of
. As
increases, once the particles are repelled, it becomes
safe to turn on FEP or TI electrostatics.
In the current implementation, the electrostatic interactions of an exnihilated, or appearing, particle are linearly coupled to the simulation over the
value range of fepElecLambdaStart/tiElecLambdaStart - 1.0. At
values less than or equal to the user-defined value of fepElecLambdaStart/tiElecLambdaStart, electrostatic interactions of the exnihilated particle are fully decoupled from the simulation. Coupling of electrostatic interactions then increases linearly for increasing values of
until
=1.0, at which point electrostatic interactions of the exnihilated particle are fully coupled to the simulation.
For annihilated, or vanishing, particles the electrostatic interactions are linearly decoupled from the simulation over the
value range of 0 - (1.0 - fepElecLambdaStart/tiElecLambdaStart). At
=0 electrostatic interactions are fully coupled to the simulation, and then linearly decreased with increasing
such that at
values greater than or equal to (1.0 - fepElecLambdaStart/tiElecLambdaStart) electrostatic interactions are completely decoupled from the simulation. Two examples, shown in Figure 10, describe the relationship between the user-defined value of
and the coupling of electrostatic or vdW interactions to the simulation.
Figure:
Relationship of user-defined
to coupling of electrostatic or vdW interactions to a simulation, given specific values of elecLambdaStart or vdwLambdaEnd.
 |
- fepVdwLambdaEnd / tiVdwLambdaEnd
Value of
to cancel van der Waals interactions
Acceptable Values: positive decimal
Default Value: 1.0
Description: If the above fepElecLambdaStart/tiElecLambdaStart option is being used, it may be further
desirable to separate the scaling of van der Waals and electrostatic
interactions. fepVdwLambdaEnd/tiVdwLambdaEnd sets the value of
above which
all vdW interactions are fully enabled for exnihilated particles.
For an exnihilated particle, vdW interactions are fully decoupled at
=0. The coupling of vdW interactions to the simulation is then increased with increasing values of
such that at values of
greater than or equal to fepVdwLambdaEnd/tiVdwLambdaEnd the vdW interactions of the exnihilated particle are fully coupled to the simulation.
For an annihilated particle, vdW interactions are completely coupled to the simulation at
=0. This coupling linearly decreases for
values between 1.0 and (1 - fepVdwLambdaEnd/tiVdwLambdaEnd). For
values greater than or equal to (1 - fepVdwLambdaEnd/tiVdwLambdaEnd), vdW interactions of the annihilated particle are fully decoupled from the simulation.
- decouple / decouple
Disable scaling of nonbonded interactions within alchemical partitions
Acceptable Values: on or off
Default Value: off
Description: With decouple set to on,
only nonbonded interactions of perturbed, incoming and outgoing atoms with
their environment are scaled, while interactions within the subset of perturbed
atoms are preserved. On the contrary, if decouple is set to off, interactions within the perturbed subset of atoms are also scaled and
contribute to the cumulative free energy. In most calculations, intramolecular
annihilation free energies are not particularly informative, and decoupling
ought to be preferred. Under certain circumstances, it may, however, be
desirable to scale intramolecular interactions, provided that the latter are
appropriately accounted for in the thermodynamic cycle [13].
Next: Examples of input files
Up: Alchemical Free Energy Methods1
Previous: Theoretical Background
Contents
Index
namd@ks.uiuc.edu