FUNNEL
This is part of the funnel module
It is only available if you configure PLUMED with ./configure –enable-modules=funnel . Furthermore, this feature is still being developed so take care when using it and report any problems on the mailing list.

Calculate a funnel-shape restraint potential that is defined on a grid that is read during the setup.

If the input file is not already present, it will create one with the name specified in the FILE flag. The potential has a two-dimensional resolution since it has been devised to be used with the two components of FUNNEL_PS (i.e., fps.lp and fps.ld) and it is divided in two sections, a cone shape attached to a cylindrical one. The user can customize the shape of both the sections by modifying a number of flags. In particular the cone section of the funnel is calculated with the following formula:

\[ MAX_Z=R_{cyl} + tg_{alpha} * (z_{cc} - MIN_S) \]

where \( MAX_Z \) is the radius of the cone base, \( R_{cyl} \) is the radius of the cylinder part, \( tg_{alpha} \) is the angle regulating how steep the cone is, \( z_{cc} \) is the switching point between cone and cylinder, and \( MIN_S \) is the lowest possible value assumed by fps.lp of FUNNEL_PS. As for the cylinder, it starts from the value of \( z_{cc} \) and stops at the value of \( MAX_S \) with a section of \( pi*r_{cyl}^2 \).

There is the option of transforming the cone region into a sphere with the use of the SPHERE flag. In this case, the new shape will have a radius of \( z_{cc} \). It might be necessary tuning the SAFETY option to select how much the potential extends from the sphere.

Examples

The following is an input for a calculation with a funnel potential that is defined in the file BIAS and that acts on the collective variables defined by FUNNEL_PS.

Click on the labels of the actions for more information on what each action computes
tested on master
lig: COM 
ATOMS
the list of atoms which are involved the virtual atom's definition.
=3221,3224,3225,3228,3229,3231,3233,3235,3237 fps: FUNNEL_PS
LIGAND
This MUST be a single atom, normally the COM of the ligand.
=lig
REFERENCE
compulsory keyword a file in pdb format containing the structure you would like to align.
=start.pdb
ANCHOR
Closest protein atom to the ligand, picked to avoid pbc problems during the simulation.
=2472
POINTS
compulsory keyword 6 values defining x, y, and z of the 2 points used to construct the line.
=4.724,5.369,4.069,4.597,5.721,4.343 funnel: FUNNEL
ARG
the input for this action is the scalar output from one or more other actions.
=fps.lp,fps.ld
ZCC
compulsory keyword ( default=ZCC ) switching point between cylinder and cone
=1.8
ALPHA
angle to change the width of the cone section
=0.55
RCYL
radius of the cylindrical section
=0.1
MINS
minimum value assumed by fps.lp,
=-0.5
MAXS
compulsory keyword ( default=MAXS ) maximum value assumed by fps.lp
=3.7
KAPPA
constant to be used for the funnel-shape restraint potential
=35100
NBINS
number of bins along fps.lp
=500
NBINZ
number of bins along fps.ld
=500
FILE
compulsory keyword name of the Funnel potential file
=BIAS

The BIAS will then look something like this:

#! FIELDS fps.lp fps.ld funnel.bias der_fps.lp der_fps.ld
#! SET min_fps.lp -0.500000
#! SET max_fps.lp 3.700000
#! SET nbins_fps.lp 500.000000
#! SET periodic_fps.lp false
#! SET min_fps.ld 0.000000
#! SET max_fps.ld 1.510142
#! SET nbins_fps.ld 500.000000
#! SET periodic_fps.ld false
    -0.500000      0.000000      0.000000      0.000000      0.000000
    -0.500000      0.003020      0.000000      0.000000      0.000000
    -0.500000      0.006041      0.000000      0.000000      0.000000
    -0.500000      0.009061      0.000000      0.000000      0.000000
    -0.500000      0.012081      0.000000      0.000000      0.000000
    -0.500000      0.015101      0.000000      0.000000      0.000000

The Funnel potential should always be used in combination with the collective variable FUNNEL_PS, since it is constructed to take as inputs fps.lp and fps.ld (the former linepos and linedist of Funnel-Metadynamics [FM]). In the first block of data the value of fps.lp (the value in the first column) is kept fixed and the value of the function is given at 500 equally spaced values for fps.ld between 0 and 1.51. In the second block of data fps.lp is fixed at \(-0.5 + \frac{4.2}{500}\) and the value of the function is given at 500 equally spaced values for fps.ld between 0 and 1.51. In the third block of data the same is done but fps.lp is fixed at \(-0.5 + \frac{8.4}{100}\) and so on until you get to the five hundredth block of data where fps.lp is fixed at \(3.7\).

It is possible to switch the shape of the cone region, transforming it in a sphere, with the flag SPHERE.

Click on the labels of the actions for more information on what each action computes
tested on master
lig: COM 
ATOMS
the list of atoms which are involved the virtual atom's definition.
=545,546,547,548,549,550,551,552,553 fps: FUNNEL_PS
LIGAND
This MUST be a single atom, normally the COM of the ligand.
=lig
REFERENCE
compulsory keyword a file in pdb format containing the structure you would like to align.
=ref.pdb
ANCHOR
Closest protein atom to the ligand, picked to avoid pbc problems during the simulation.
=52
POINTS
compulsory keyword 6 values defining x, y, and z of the 2 points used to construct the line.
=2.793,3.696,3.942,3.607,4.298,3.452 funnel: FUNNEL
ARG
the input for this action is the scalar output from one or more other actions.
=fps.lp,fps.ld
ZCC
compulsory keyword ( default=ZCC ) switching point between cylinder and cone
=4.0
RCYL
radius of the cylindrical section
=0.1
MINS
minimum value assumed by fps.lp,
=0.2
MAXS
compulsory keyword ( default=MAXS ) maximum value assumed by fps.lp
=4.9
KAPPA
constant to be used for the funnel-shape restraint potential
=100000
NBINS
number of bins along fps.lp
=500
NBINZ
number of bins along fps.ld
=500
SPHERE
( default=off ) The Funnel potential including the binding site can be spherical instead of a cone
SAFETY
To be used in case the SPHERE flag is chosen, it regulates how much the potential extends (in nm)
=1.0
FILE
compulsory keyword name of the Funnel potential file
=BIAS
Glossary of keywords and components
Description of components

By default this Action calculates the following quantities. These quantities can be referenced elsewhere in the input by using this Action's label followed by a dot and the name of the quantity required from the list below.

Quantity Description
bias the instantaneous value of the bias potential
Compulsory keywords
SCALE ( default=1.0 ) a factor that multiplies the external potential, useful to invert free energies
MAXS ( default=MAXS ) maximum value assumed by fps.lp
ZCC ( default=ZCC ) switching point between cylinder and cone
FILE name of the Funnel potential file
Options
NUMERICAL_DERIVATIVES ( default=off ) calculate the derivatives for these quantities numerically
NOSPLINE ( default=off ) specifies that no spline interpolation is to be used when calculating the energy and forces due to the external potential
SPARSE ( default=off ) specifies that the external potential uses a sparse grid
SPHERE ( default=off ) The Funnel potential including the binding site can be spherical instead of a cone
WALKERS_MPI

( default=off ) To be used when gromacs + multiple walkers are used

ARG the input for this action is the scalar output from one or more other actions. The particular scalars that you will use are referenced using the label of the action. If the label appears on its own then it is assumed that the Action calculates a single scalar value. The value of this scalar is thus used as the input to this new action. If * or *.* appears the scalars calculated by all the proceeding actions in the input file are taken. Some actions have multi-component outputs and each component of the output has a specific label. For example a DISTANCE action labelled dist may have three components x, y and z. To take just the x component you should use dist.x, if you wish to take all three components then use dist.*.More information on the referencing of Actions can be found in the section of the manual on the PLUMED Getting Started. Scalar values can also be referenced using POSIX regular expressions as detailed in the section on Regular Expressions. To use this feature you you must compile PLUMED with the appropriate flag. You can use multiple instances of this keyword i.e. ARG1, ARG2, ARG3...
NBINS number of bins along fps.lp
NBINZ number of bins along fps.ld
MINS minimum value assumed by fps.lp, if the ligand is able to go beyond this value the simulation will crash
KAPPA constant to be used for the funnel-shape restraint potential
RCYL radius of the cylindrical section
SAFETY To be used in case the SPHERE flag is chosen, it regulates how much the potential extends (in nm)
SLOPE Adjust the behavior of the potential outside the funnel, greater values than 1.0 will tend to push the ligand more towards the cylinder and vice versa
ALPHA angle to change the width of the cone section