Examples of input files for running alchemical free energy calculations

The first example illustrates the use of TCL scripting for running an alchemical transformation with the FEP feature of NAMD. In this calculation, $\lambda$ is changed continuously from 0 to 1 by increments of $\delta \lambda$ = 0.1.

fep On fepFile ion.fep fepCol X fepOutfile ion.fepout fepOutFreq 5 fepEquilSteps 5000 set Lambda0 0.0 set dLambda 0.1 while {$Lambda0 <= 1.0} { lambda $Lambda0 set Lambda0 [expr \$Lambda0 + \$dLambda] lambda2 $Lambda0 run 10000 }

Turn FEP functionality on. File containing the information about growing/shrinking atoms described in column X. Output file containing the free energy. Frequency at which fepOutFreq is updated. Number of equilibration steps per $\lambda$-state. Starting value of $\lambda$. Increment of $\lambda$, i.e.  $\delta \lambda$. TCL script to increment $\lambda$: (1) set lambda value; (2) increment $\lambda$; (3) set lambda2 value; (4) run 10,000 MD steps.

The user should be reminded that by setting run 10000, 10,000 MD steps will be performed, which includes the preliminary fepEquilSteps equilibration steps. This means that here, the ensemble average of equation (30) will be computed over 5,000 MD steps.

Alternatively, $\lambda$-states may be declared explicitly, avoiding the use of TCL scripting:

lambda 0.0 lambda2 0.1 run 10000

(1) set lambda value; (2) set lambda2 value; (3) run 10,000 MD steps.

This option is generally preferred to set up windows of diminishing widths as $\lambda \rightarrow$ 0 or 1 -- a way to circumvent end-point singularities caused by appearing atoms that may clash with their surroundings.

The following second input is proposed for the measuring via TI the free energy of a particle insertion.

    thermInt      On             # Enable thermodynamic integration
    tiFile        ion.alch.pdb   # PDB file with perturbation flags
    tiCol         B              # Perturbation flags in Beta column
    tiOutfile     ion.ti.out
    tiOutFreq     5
    tiEquilSteps  5000

    tiVdWShiftCoeff    1         # Enable soft-core vdW potential
    tiElecLambdaStart  0.1       # Introduce electrostatics for lambda > 0.1
    tiLambda 0
    run 10000
    tiLambda 0.00001
    run 10000
    tiLambda 0.0001
    run 10000
    tiLambda 0.001
    run 10000
    tiLambda 0.01
    run 10000

    set Lambda           0.1

    while {$Lambda <= 0.9} {
      tiLambda $Lambda
      run 10000
      set Lambda [expr $Lambda + 0.1]
    }

    tiLambda 0.99
    run 10000
    tiLambda 0.999
    run 10000
    tiLambda 0.9999
    run 10000
    tiLambda 0.99999
    run 10000
    tiLambda 1
    run 10000

Robust sampling of the free energy of particle insertion is enabled by the use of soft-core van der Waals scaling with the VdWShiftCoeff parameter, delayed introduction of electrostatics with a non-zero tiElecLambdaStart value, and very gradual scaling of $\lambda$ towards its end points.