[Installation]

1. download the file "ghecom-src-[date].tar.gz" file.

2. tar zxvf ghecom-src-[date].tar.gz

3. cd src

4. make

[Summary of various spaces identified by ghecom program ]

Notation for mathematical morphology

X	VdW volume of protein
P	large (external) probe
S	small (internal) probe
Pk	k-th large (external) probe

-	erosion
+	dilation
*	closing. X * P = (X + P) - P
o	opening. X o P = (X - P) + P
IX[Y]	return Y only if Y access to the outside around X, otherwise return nothing
Ck[Y]	k-th connected coponent of Y
Cout[Y]	The component of Y connected to the outside.

[How to use the ghecom program]

1. Simple Pocket Detection (MODE='P')

   A pocket is defined as a space where small probe S can enter, but a large probe P cannot.

   Standard Usage

   ghecom -M P -ipdb [input_pdbfile] -opocpdb [output_pocket_grid_pdbfile]

   For example, to find the pocket for the pdbfile "3wz8":

   ghecom -M P -ipdb pdb3wz8.ent -opocpdb 3wz8_pock.pdb

   Options for input PDB file are summarized elsewhere.

   Options for grid pocket calculation:
   

   • -gw : Grid width [0.800000]
   • -rs : Radius for small probe spheres [1.870000]
   • -rl : Radius for large probe spheres [6.000000]
   • -clus: clustering pockets ('T' or 'F') [T]

   Options for output

   • -opocpdb: Output file for Grid Points of Pocket in PDB[]

     If -clus T, the rank of clusters are described in residue number and model number in the PDB file.

   • -opocmap: Output file for Pocket in 3D density map (*.map) []

     If -clus F, only one map is generated. If -clus T, each cluster is written in a separated map file. For example, the options -clus T -opocmap out.map are assigned and 4 pocket clusters are identified, then the 4 files, out_1.map, out_2.map, out_3.map, and out_4.map are generated.

   • -opdb : Output receptor PDB file with Cluster Number[]

   Options to obtain spherical (non-grid) probes:

   • -oprb: Output PDB file for 3-contacting spherical probes []
   • -oprd: Output PDB file for 3-contacting spherical probes in DOCK sphere format []

   3wx8 chain A and the ligand IXV	3wx8_P.pdb colored by model number	3wx8_P_1.map(red), 3wx8_P_2.map(green), and 3wx8_P_3.map(blue)
   COMMAND: ghecom -M P -ipdb pdb3wz8.ent -ch A -rs 1.87 -rl 10.0 -opocpdb 3wz8_P.pdb -opocmap 3wz8_P.map rendered by UCSF Chimera

2. Multi-scale Pocket Detection (MODE='M')

   A multi-scale pocket is defined using K large probes {P_k}.

   Standard Usage

   ghecom -M M -ipdb [input_pdbfile] -opocpdb [output_multi_scale_pocket_grid_pdbfile]

   ghecom -M M -ipdb [input_pdbfile] -opocpdb [output_multi_scale_pocket_grid_pdbfile] -opdb [out_receptor_file_with_Rinaccess]

   For example, to find the multi-scale pocket for the pdbfile "3wz8":

   ghecom pdb3wz8.ent -M M -opoc 3wz8_multi_pock.pdb -opdb 3wz8_multi_recep.pdb

   Options for input PDB file are summarized elsewhere.

   Other options are summarized as follows( A string in the blackets [] is the default value):

   • -gw : Grid width [0.800000]
   • -rs : Radius for small probe spheres [1.870000]
   • -rli : Radius for min_large probe spheres [2.000000]
   • -rlx : Radius for max_large probe spheres [10.000000]
   • -br : bin of large probe radius for MODE 'M' [0.500000]
   • -clus: clustering pockets ('T' or 'F') [T]

   Output options as follows:

   • -opocpdb: Output Pocket in PDB file[].
     Residue number and tFactor indicate the size of large probe (i in P[i]). Chain ID and MODEL number indicate the index of the pocket clusters.

   • -opocmap: Output Pocket in 3D density map file (*.map) [].
     A density values indicate the size of large probe (i in P[i]).

   • -opdb : Output receptor PDB file[]
     Pocketness are described as tFactor.

   • -ores: Output Rediue-based property file with calculated Rinaceess/Pocketness[]

   If a user wants to calculate the Rinaccess(shallowness) value for binding ligands, following two options should be added.

   • -iligpdb : Input ligand PDB file for Rinaccess calculation (only for MODE 'M') []
   • -oligpdb : Output ligand PDB file with calcualted Rinaccess (only for MODE 'M') []

   Options to obtain spherical (non-grid) probes:

   • -oprb: Output PDB file for 3-contacting spherical probes []
   • -oprd: Output PDB file for 3-contacting spherical probes in DOCK sphere format []

   3wx8 chain A and the ligand IXV	3wx8_M.pdb colored by bfactor (depth)	3wx8_M_rec.pdb colored by bfactor (pocketness)	3wx8_M.map
   COMMAND: ghecom -M M -ipdb pdb3wz8.ent -ch A -opocpdb 3wz8_M.pdb -opocmap 3wz8_M.map -opdb 3wz8_M_rec.pdb -ores 3wx8_M_res.txt rendered by UCSF Chimera

   Residue-based pocketness drawn from "3wx8_M_res.txt". red: 1st largest cluster, green:2nd largest cluster, blue 3rd largest cluster.

3. Cavity in the molecule (MODE='V')

   The "cavity" is difined as the space where a probe P cannot enter from outside.

   Its standard usage is as follows:

   ghecom -M V -ipdb [pdbfile] -rl [radius_of_probe] -opocpdb [cavity grid file in PDB]

   For example, to find the cavity for the water in the pdb "1mbd":
   ghecom -M V -ipdb pdb1mbd.ent -M V -rl 1.4 -gw 0.5 -opocpdb cavity_grid.pdb

   For another example, to find the big cavity for the GroEL/ES (PDBID:1aon):
   ghecom -M V -ipdb pdb1aon.ent -M V -rl 20 -gw 4.0 -opocpdb cavity_grid.pdb

   Options for input PDB file are summarized elsewhere. Options for grid pocket calculation:
   

   • -gw : Grid width [0.800000]
   • -rs : Radius for small probe spheres [1.870000]
   • -rl : Radius for large probe spheres [6.000000]
   • -clus: clustering pockets ('T' or 'F') [T]

   Options for outputs

   • -opocpdb: Output Pocket in PDB file[]
   • -opocmap: Output Pocket in 3D density map file (*.map) []
   • -opdb : Output receptor PDB file with Cluster Number[]

4. Cave pocket (MODE='CP')

   The "cave pocket" is difined as the space where an internal probe S can enter, but an external probe P cannot enter from outside.

   Its standard usage is as follows:

   ghecom -M CP -ipdb [pdbfile] -rl [radius_of_external_probe] -rs [radius_internal_robe] -opocpdb [cavity grid file in PDB]

   For example, to find the big innner pocket for the GroEL/ES (PDBID:1aon):
   ghecom -M CP -ipdb pdb1aon.ent -M CP -rl 25 -rs 10 -gw 4 -opocpdb pockgrid.pdb

   For another example, to find the small binding pocket for the AMP (PDBID:12as):
   ghecom -M CP -ipdb pdb12as.ent -ch A -gw 1.0 -rl 3 -rs 1.87 -opocpdb poc.pdb

   The options for the cavepocket are quite similar to those for the pocket.

   Options for input PDB file are summarized elsewhere.

   Options for grid pocket calculation:
   

   • -gw : Grid width [0.800000]
   • -rs : Radius for small probe spheres [1.870000]
   • -rl : Radius for large probe spheres [6.000000]
   • -clus: clustering pockets ('T' or 'F') [T]

   Options for outputs:

   • -opocpdb: Output Pocket in PDB file[]
   • -opocmap: Output Pocket in 3D density map file (*.map) []
   • -opdb : Output receptor PDB file with Cluster Number[]

   Cavity:Rlarge=20 [1aon_V.pdb]	Cavity:Rlarge=20, [1aon_V.map]
   COMMAND: ghecom -M V -ipdb pdb1aon.ent -gw 4.0 -rl 20 -clus F -opocpdb 1aon_V.pdb -opocmap 1aon_V.map
   Pocket:Rlarge=25, Rsmall=10 [1aon_P.pdb]	Pocket:Rlarge=25, Rsmall=10 [1aon_P.map]
   COMMAND:ghecom -M P -ipdb pdb1aon.ent -gw 4.0 -rl 25 -rs 10 -clus F -opocpdb 1aon_P.pdb -opocmap 1aon_P.map
   Cave Pocket:Rlarge=25, Rsmall=10 [1aon_CP.pdb]	Cave Pocket:Rlarge=25, Rsmall=10 [1aon_CP.map]
   COMMAND:ghecom -M CP -ipdb pdb1aon.ent -gw 4.0 -rl 25 -rs 10 -clus F -opocpdb 1aon_CP.pdb -opocmap 1aon_CP.map rendered by UCSF Chimera

[Common options for GHECOM]

• Options for input PDB file
  
  • -ipdb : input PDB file []
  • -icif : input mmCIF file []
  • -ch : ChainID for target pdbfile [-]
  • -atmhet: Read only ATOM 'A', only HETATM 'H', both 'B' [A]
  • -hetpep2atm : Change HETATM residues with N_CA_C_O to ATOM ('T' or 'F') [T]
  • -asym_id: asym_id for target pdbfile (only for -icif) []
  • -assembly: assembly_id for mmCIF file (only for -icif) []
  • -rvdw : vwRadius type for input PDB file 'C'hothia1976 'B'ondi1964, 'O'ccupancy, 'U'nified [C]
    If -rvdw O is assigned, radius is taken from Occupancy value in PDB file.
• Options for outputs
  
  • -ovdwpdb : Output VdW protein 3D grid PDB file
  • -ovdwmap : Output VdW protein 3D density map file

[References]

• Kawabata T. Detection of multi-scale pockets on protein surfaces using mathematical morphology. Proteins, 2010,78, 1195-1121. [PubMed]
  (The primary article to be cited for using the program "ghecom".)

• Kawabata T, Go N. Detection of pockets on protein surfaces using small and large probe spheres to find putative ligand binding sites. Proteins, 2007, 68,516-529. [PubMed]
  (This article is the reference of the "phecom" program. The basic pocket idea using small and large probes is described in this article.)

• Kawabata T. Detection of cave pockets in large molecules: Spaces into which internal probes can enter, but external probes from outside cannot. Biophys Physicobiol. 2019; 16: 391-406. [PubMed]

• Masuya M, Doi J. Detection and geometric modeling of molecular surfaces and cavities using digital mathmatical morphological operations. Journal of Molecular Graphics, Vol 13, 331-336, (1995) [PubMed]
  ( The algorithm using mathematical morphology with small and large probes is firstly proposed by this article.)

• Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. J Comput Chem. 2004 Oct;25(13):1605-12. UCSF Chimera--a visualization system for exploratory research and analysis.