Parameters¶

SEED user-modifiable parameters are contained in two main input files. | The file seed.inp contains the most frequently modified Input Parameters as they regard a specific SEED run (path and name of structural input files, list of residues forming the binding pocket, switch between polar and apolar docking, …).

The Parameter File seed.par contains less frequently modified input/output options, parameters for docking, energy and clustering. Modification of most of these parameters is recommended only to advanced users who wish to fine tune the energy model.

Input Parameters¶

Here we define all the parameters of the seed.inp file.

i1: name of parameter file (seed.par)

i2: name of coordinate file for the receptor (in SYBYL mol2 format)

i3: Binding site residue list.

First line: number of residues in the binding site.

Following lines: residue indices (one per line).

Note that residues are renumbered sequentially starting from 1 within SEED and the residue index refers to this new numbering; if for example ARG38 is the first residue of the protein, its index is 1 and not 38. The SEED residue indices can be retrieved from seed.out after the line Data for the receptor :. To avoid ambiguity we recommend to renumber the residues starting from 1 in the input file. Binding site metal ions have to be in the list as well.

i4: List of points (e.g. ligand heavy atoms of a known ligand-receptor complex structure) in the binding site used to select polar and apolar receptor vectors which satisfy the angle criterion (see Angle criterion) and discard vectors pointing outside of the binding site.

First line: number of points (0: no removal of vectors using the angle criterion).

Following lines: coordinates of the points (one point per line).

i5: Vectors for the metal ions in the binding site.

Make sure that the residue number of the metal is in the binding site residue list.

First line: total number of coordination points.

Following lines: atom number of metal / x y z of coordination point (vector extremity)

i6: Spherical cutoff for docking:

coordinates of the center and radius of a sphere in which the geometry center of the fragment position must be in order to be accepted. This filter can be discarded by selecting n instead of y as first value.

y,``n`` / sphere center / sphere radius

i7: Fragment library specifications

First line: one character specifying the running mode of SEED: Docking running mode (d) or only Energy evaluation mode (e).

Following lines: the first column contains the path of the fragment mol2 file and the second column allows the selection of apolar, polar docking or both (a, p, b). The fragment position is accepted if the total energy (according to the fast energy model) is smaller than a cutoff given in the third column. The second Clustering is applied on the poses for which the binding energy of the cluster representative is smaller than a cutoff value specified in the 4th column. In summary:

Fragment library filename / apolar docking, polar docking, or both (a, p, b) / energy cutoff in kcal/mol / 2nd clustering cutoff in kcal/mol

As you do not need to modify all the parameters and in most of the cases default values will give good results, we recommend not to write an input file from scratch, but to modify a default template. You can do this here through the Parameter File Generator.

Parameter File¶

Here we define all the parameters of the seed.par file.

p1: Dielectric constant of the solute (receptor and fragment)

p2: Ratio of kept vectors for docking : polar / apolar

p3: Output control for structure files (two values on the same line).

First value: write *_clus.mol2 file (y/n)

Second value: write *_best.mol2 file (y/n)

p4: Output control for energy table files (two values on the same line).

First value: write *_clus.dat summary table file (y/n)

Second value: write *_best.dat summary table file (y/n)

p5: Maximum number of saved clusters and poses (two values on the same line).

First value: maximum number of cluster members saved in *_clus* output files. Note that this value determines the maximum number of poses per cluster that go through slow energy evaluation. Second value: maximum number of poses saved in *_best* output files.

p6: Filename for output log file. This is the main SEED output file (seed.out).

The docked fragments are saved in the directory ./outputs

p7: write (w) or read (r) Coulombic grid / grid filename

p8: write (w) or read (r) van der Waals grid / grid filename

p9: write (w) or read (r) receptor desolvation grid / grid filename

p10: Bump checking: used only for slow energy evaluation (three values)

n x atoms = maximum tolerated bumps /

scaling factor for interatomic distance /

severe overlap factor (beta factor in PROTEINS paper)

p11: van der Waals energy cutoff (kcal/mol): this is used as bump checking for the fast energy model.

p12: Angle (deg) and number of points on the sphere around the ideal hydrogen bonding vector direction.

p13: Number of fragment rotations around each axis.

p14

Settings for the reduction of the seeding vectors (four values).

angle_rmin if distance <= (multipl_fact_rmin*minDist)
angle_rmax if distance >= (multipl_fact_rmax*maxDist)
linear dependence (range between angle_rmin and angle_rmax) for other distances

p15: Van der Waals probe radius for removal of the receptor polar vectors.

p16: Settings for the Coulombic term in the fast energy model (three values).

1 = distance dependent dielectric / grid margin / grid spacing

p17: Settings for the van der Waals term in the fast energy model (two values).

grid margin / grid spacing

p18: Settings for the van der Waals accurate energy model (two values).

nonbonding cutoff / grid spacing

Note that the Coulombic cutoff for formal charges is automatically set to 1.3 x van_der_Waals_cutoff

p19: Multiplicative factor (k) for apolar docking to skip evaluation of electrostatics. The van der Waals energy cutoff is:

k x Number of fragment atoms, including hydrogen atoms

p20: Settings for the solvation grid (two values):

grid margin / grid spacing

p21: Settings for the solvation term evaluation (three values):

water radius for solvation / number of points per sphere to generate SAS / solvent dielectric constant

p22: Setting for the Hydrophobicity maps (five values):

point densities (A^-2) on the SAS for apolar vectors on the receptor / on the fragment / probe radius to generate SAS for apolar vectors / scaling factor for desolvation and / van der Waals interactions

p23: Scaling factors for fast and also accurate energy evaluation (four values): van der Waals / electrostatic interaction / receptor desolvation / fragment desolvation

Clustering parameters¶

The clustering with GSEAL proceeds in two steps: the first clustering yields large clusters which contain almost overlapping as well as more distant fragments; the second clustering is done on each cluster found in the first clustering to eliminate fragments which are very close in space.

p24: Non-default similarity weight factors (150 atom elements) for GSEAL:

First line: 0 or number of non-default elements

Following lines: list (first element number / second element number / value )

p25: Parameters for first clustering (overall clustering):

GSEAL similarity exponential factor / cutoff factor

p26: Parameters for second clustering (to discard redundant positions):

GSEAL similarity exponential factor / cutoff factor

p27: Maximal number of poses to be clustered

p28: Setting for the amount of information to be written to the output seed.out:

Maximum number of lines to be written in the output file for the sorted energies and the two clustering procedures /

print level (0 = lean, 1 = adds sorting before postprocessing, 2 = adds 2nd clustering).

Monte Carlo parameters¶

mc1: Perform MC refinement? (y/n)
mc2: Starting temperature of MC run.
mc3: Maximum rigid body translation step (in Angstrom): coarse (1st value)

and fine (2nd value) moves.
mc4: Maximum rigid body rotation step (in degrees): coarse (1st value)

and fine (2nd value) moves.
mc5: MC move set frequencies:

Frequency \(p\) of rigid body rotation moves (the frequency of

rigid body translation move will be \(q = 1 - p\)).
mc6: Relative frequency (w.r.t. the number of rotation moves) of fine rotation moves.
mc7: Relative frequency (w.r.t. the number of translation move) of fine translation moves.
mc8: Number of steps \(N_{out}\) of the outer MC chain (1st value). /

Number of steps \(N_{in}\) of the inner MC chain (2nd value).
mc9: Annealing parameter \(\alpha\).
mc10: Seed for the pseudo-random number generator used by the MC sampler.

Force field parameters¶

p29: Van der Waals radius and energy minimum (absolute value).

First line: number of records

Following lines: each record contains five values:

sequential index / atom type / element number / van der Waals radius / van der Waals energy minimum

p30

Hydrogen bond distances between donor and acceptor.
First  line: Default distance for all atom and element types.
First block:

First line: number of records
Following lines: element number i / element number j / donor-acceptor distance

Second block:

First line: number of records
Following lines: atom type i / atom type j / donor-acceptor distance

p31: List of relative atomic weights.

First line: number of elements (without element 0)

element name / element number / atomic weight

Parameter File Generator¶

The parameter file generator helps you preparing the input parameter files for a SEED run (seed.inp and seed.par). You can load a template with predefined default values, edit the user-specific information and save it.

Here you can edit the file with user-specific information. Fields you necessarily have to edit are marked by XXXX

File name