Hybrid methods

Hybrid methods

Bridging the resolution gap with hybrid methods
Protein modeling

Protein modeling

Modeling protein structures and their interactions
Multiscale dynamics

Multiscale dynamics

Exploring the macromolecular biomachines dynamics
Drug Discovery

Drug Discovery

Computer-aided rational drug design and discovery

Here we give a brief overview of the necessary commands to run FRODOCK, but we strongly encourage to follow the tutorials. Right now, there are four different executables: 

  • frodockgrid to pre-calculate the protein potential maps.
  • frodock to perform the protein protein docking 6D exhaustive search.
  • frodockcluster  for clustering frodock's raw predictions.
  • frodockview for displaying solutions and creating pdb solutions.

This user guide describes the usage of these FRODOCK components.

FRODOCKGRID - precomputing potential maps


To create the potential maps that will be used for scoring during the docking process, enter the following command at the prompt:

frodockgrid <pdb>   -m <int>

where:

pdb

The initial model structure to be fitted (PDB format)

−m <int>

Type map to generate:

  • 0: [default] van der Waals potential map.

  • 1: Electrostatic potential map.

  • 2: Charge projection map.

  • 3: Desolvation potential + PDB file with ASA in Occupancy column + ASA projection map.

Basic Options


In this section, the basic options to customize the potential maps are detailed. Just add them after the minimum command shown above.

−o <string>

Volume output filename (default: frodockgrid.ccp4).

−−gs <float>

Volume output grid size in amstrongs (default: 1.0).

−t <char>

Type of interaction (used only with -m 1):

E: Enzyme/Inhibitor or Enzyme/substrate.

A: Antobody/Antigen.

O: Others(Default).

−−wr <float>

Water probe radius in amstrongs. To be used only when -m={0,3} (default: 1.4).

−−sr <float>

Desolvation probe radius in amstrongs. To be used only when -m={0,3} (default: 1.95).

−h

Displays usage information and exits.

Advanced options


Only for expert users!

−−hyd

Consider hydrogen in the creation of the potential map.

−−fp <int>

Forcefield parameters:

  • 0: [default] CHARMM

  • 1: ICM

  • 2: EEF1

  • 3: Sybil

−−an <int>

Atom name convention:

  • 0: [default] IUPAC

  • 1: PDB

−−rm <float>

Van der Walls radius modification (default: 1. DEPRECATED)

−p

Use forces in fact column of the PDB file

 

FRODOCK - Docking process


To perform a basic shape (van de Waals) docking enter the following command at the prompt:

frodock <recept_pdb> <ligand_pdb> --E 0

Alternatively, by removing the --E flag the electrostaics can be considered. You could include the vdW and electrostatics precalculated maps using -w and -e <string> options, respectively. These simple docking alternatives can be useful as a first aproximation.The recommended option is to include vdw, electrostatic and desolvation terms, i.e.:

frodock rec_ASA.pdb lig_ASA.pdb −d lig_sol.cpp4,rec_sol.cpp4

When using desolvation it is madatory ligand and receptor pdb input files with the atom ASA values in the Occupancy column. These files are standard output of frodockgrid, please do not forget to use them instead of the original ones. Exploiting pre-calculations to gain efficiency, an equivalent command line will be:

frodock rec_ASA.pdb lig_ASA.pdb  −w rec_vdw.cpp4 −e rec_ele.cpp4 −d lig_solv.cpp4,rec_solv.cpp4


where:

<recept_pdb>

The receptor structure PDB.

<ligand_pdb>

The ligand structure PDB (the smallest one recommended).

−w <string>

vdW receptor potential file (default: Created from receptor pdb file).

−e <string>

Electrostatic receptor map

−−E <float>

Electrostatic term weight (default: 0.3)

−d <string>

Desolvation potential maps for receptor and ligand (syntax: -d receptor_map.ccp4,ligand_map.ccp4).

−−D <float>

Desolvation term weight (default: 0.5)

Basic Options


In this section, the basic options to customize the docking process are detailed.

−o <string>

Solutions output filename (default: frodock_output.dat).

−−bw <int>

Bandwidth in spherical harmonic representation. Define rotational stepsize (default: 32. Rotational stepsize ~6°)

−−lmax <float>

External Mask reduction ratio. (default: 0.23)

−−lmin <float>

Internal Mask reduction ratio. (default: 0.43)

−−th <float>

Electrostatic map threshold. (default: 10.0)

−−lw <float>

Width between spherical layers in amstrongs. (default: 1.0)

−−st <float>

Translational search stepsize in amstrongs. (default: 2.0)

−h

Displays usage information and exits.

Advanced options


Only for expert users!

−W <float>

Van der Waals term weight (default: 1.0)

−−np <int>

Number of solutions stored per traslational position. (default: 4)

−−rd <float>

Minimal rotational distance allowed between close solutions in degrees. (default: 12.0)

−−nt <int>

Number of solutions stored in the search. (default: unlimited)

−−td <float>

Maximal translational distance to consider close solutions in grid units. (default: 0)

−a<string>

Receptor and ligand ASA maps (default: created from receptor and ligand pdb files if Desolvation potential used. Syntax: -a asa_receptor,asa_ligand).

−−around <string>

translational search restricted to a region around a point defined in "x,y,z" format.

−−nover

Show no messages.

−−fp <int>

Forcefield terms employed:

0: Rosseta (default)

1: ICM

2: EEF1

3: Sybil

 

FRODOCKCLUSTER - Sort and cluster frodock output file


To sort and cluster the docking solutions, enter the following command at the prompt:

frodockcluster <data> <pdb

where:

<data>

Frodock solutions data filename. (required)

<pdb>

Ligand pdb filename. (required)

 

−o <string>

Clustered solution output Frodock filename (default: frodockcluster.dat)

−d <float>

RMSD distance between clusters (default: 5.0).

−−nc <int>

Maximum number of clusters to generate (default: unlimited).

−h

Displays usage information and exits.

Only for real expert users!

−−ns <int>

Limit the number of solutions employed (default all the solutions are used)

−e

Input solution file is a evaluated Frodock file.

−−ns

The solutions in input file are sorted by correlation (Skip sort operation).

−c <float>

Ratio of maximal correlation used to define correlation interval in clusters (default: 1.0).

 

FRODOCKVIEW - Show and create pdb solutions


To show docking solutions and create resulting PDBs, enter the following command at the prompt:

frodockview <input>

where:

<input>

Frodock solutions input filename (required)

Other options

−r <string>

Range of solutions showed (default: all solutions).

−p <string>

Generate pdb files applying solutions coordinates showed over Ligand pdb file (default: No files created

−−size

Show the total number of solution in file.

−e

Input file is a Frodock evaluated file.

−d

Disable solution files creation

−f <string>

Reference PDB file for RMSD evaluation of solutions (Requires -p option)

−h

Displays usage information and exits.