FUNNEL_PS
 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.

FUNNEL_PS implements the Funnel-Metadynamics (FM) technique in PLUMED 2.

Please read the FM [77] [106] papers to better understand the notions hereby reported.

This colvar evaluates the position of a ligand of interest with respect to a given line, built from the two points A and B, and should be used together with the FUNNEL bias. The constructed line represents the axis of the funnel-shape restraint potential, which should be placed so as to include the portion of a macromolecule (i.e., protein, DNA, etc.) that should be explored. Since it is important that the position of the line is updated based on the motion of the macromolecule during the simulation, this colvar incorporates an alignment method. The latter uses the TYPE=OPTIMAL option to remove motions due to rotation and translation of the macromolecule with respect to a reference structure, which is provided by the user. In order to accomplish the task, an optimal alignment matrix is calculated using the Kearsley [69] algorithm. The reference structure should be given as a pdb file, containing only the atoms of the macromolecule or a selection of them (e.g., the protein CA atoms of secondary structures). In contrast to the methods reported in the Distances from reference configurations, the values reported in the occupancy and beta-factor columns of the pdb file are not important since they will be overwritten and replaced by the value 1.00 during the procedure. It is important to understand that all atoms in the file will be used for the alignment, even if they display 0.00 in the occupancy column.

The ligand can be represented by one single atom or the center of mass (COM) of a group of atoms that should be provided by the user.

By default FUNNEL_PS is computed taking into account periodic boundary conditions. Since PLUMED 2.5, molecules are rebuilt using a procedure that is equivalent to that done in WHOLEMOLECULES. We note that this action is local to this colvar, thus it does not modify the coordinates stored in PLUMED. Moreover, FUNNEL_PS requires an ANCHOR atom to be specified in order to facilitate the reconstruction of periodic boundary conditions. This atom should be the closest macromolecule's atom to the ligand and it should reduce the risk of ligand "warping" in the simulation box. Nevertheless, we highly recommend to add to the PLUMED input file a custom line of WHOLEMOLECULES, in order to be sure of reconstructing the ligand together with the macromolecule (please look the examples). In this case, the user can use the NOPBC flag to turn off the internal periodic boundary condition reconstruction.

FUNNEL_PS is divided in two components (fps.lp and fps.ld) which evaluate the projection of the ligand along the funnel line and the distance from it, respectively. The values attributed to these two components are then used together with the potential file created by the FUNNEL bias to define if the ligand is within or not in the funnel-shape restraint potential. In the latter case, the potential will force the ligand to enter within the funnel boundaries.

Examples

The following input tells plumed to print the FUNNEL_PS components for the COM of a ligand. The inputs are a reference structure, which is the structure used for the alignment, the COM of the molecule we want to track, and 2 points in the Cartesian space (i.e., x, y, and z) to draw the line representing the funnel axis.

Click on the labels of the actions for more information on what each action computes
lig: COM ATOMSthe list of atoms which are involved the virtual atom's definition. =2446,2447,2448,2449,2451
fps: FUNNEL_PS REFERENCEcompulsory keyword
a file in pdb format containing the structure you would like to align. =protein.pdb LIGANDThis MUST be a single atom, normally the COM of the ligand. =lig POINTScompulsory keyword
6 values defining x, y, and z of the 2 points used to construct the line. =5.3478,-0.7278,2.4746,7.3785,6.7364,-9.3624
PRINT ARGthe input for this action is the scalar output from one or more other actions. =fps.lp,fps.ld


It is recommended to add a line to force the reconstruction of the periodic boundary conditions. In the following example, WHOLEMOLECULES was added to make sure that the ligand was reconstructed together with the protein. The list contains all the atoms reported in the start.pdb file followed by the ANCHOR atom and the ligand. All atoms should be contained in the same entity and the correct order.

Click on the labels of the actions for more information on what each action computes
WHOLEMOLECULES ENTITY0the atoms that make up a molecule that you wish to align. =54,75,212,228,239,258,311,328,348,372,383,402,421,463,487,503,519,657,674,690,714,897,914,934,953,964
974,985,1007,1018,1037,1247,1264,1283,1302,1324,1689,1708,1727,1738,1962,1984,1994,2312,2329,2349,2467,2490,2500,2517,2524,2536,
2547,2554,2569,2575,2591,2607,2635,2657,2676,2693,2700,2719,2735,2746,2770,2777,2788,2795,2805,2815,2832,2854,2868,2898,2904,
2911,2927,2948,2962,2472,3221,3224,3225,3228,3229,3231,3233,3235,3237
lig: COM ATOMSthe list of atoms which are involved the virtual atom's definition. =3221,3224,3225,3228,3229,3231,3233,3235,3237
fps: FUNNEL_PS LIGANDThis MUST be a single atom, normally the COM of the ligand. =lig REFERENCEcompulsory keyword
a file in pdb format containing the structure you would like to align. =start.pdb ANCHORClosest protein atom to the ligand, picked to avoid pbc problems during the simulation.
=2472 POINTScompulsory 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
PRINT ARGthe input for this action is the scalar output from one or more other actions. =fps.lp,fps.ld

Glossary of keywords and components
Description of components

By default the value of the calculated quantity can be referenced elsewhere in the input file by using the label of the action. Alternatively this Action can be used to calculate the following quantities by employing the keywords listed below. 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 lp the position along the funnel line ld the distance from the funnel line
The atoms involved can be specified using
 LIGAND This MUST be a single atom, normally the COM of the ligand. For more information on how to specify lists of atoms see Groups and Virtual Atoms ANCHOR Closest protein atom to the ligand, picked to avoid pbc problems during the simulation. For more information on how to specify lists of atoms see Groups and Virtual Atoms
Compulsory keywords
 REFERENCE a file in pdb format containing the structure you would like to align. POINTS 6 values defining x, y, and z of the 2 points used to construct the line. The order should be A_x,A_y,A_z,B_x,B_y,B_z.
Options
 NUMERICAL_DERIVATIVES ( default=off ) calculate the derivatives for these quantities numerically NOPBC ( default=off ) ignore the periodic boundary conditions when calculating distances SQUARED-ROOT ( default=off ) Used to initialize the creation of the alignment variable