GRAMM v1.03

Global Range Molecular Matching

GRAMM is a program for protein docking. To predict the structure of a complex, it requires only the atomic coordinates of the two molecules (no information about the binding sites is needed). The program performs an exhaustive 6-dimensional search through the relative translations and rotations of the molecules. The molecular pairs may be: two proteins, a protein and a smaller compound, two transmembrane helices, etc. GRAMM may be used for high-resolution molecules, for inaccurate structures (where only the gross structural features are known), in cases of large conformational changes, etc.

The Global RAnge Molecular Matching (GRAMM) methodology is an empirical approach to smoothing the intermolecular energy function by changing the range of the atom-atom potentials. The technique locates the area of the global minimum of intermolecular energy for structures of different accuracy. The quality of the prediction depends on the accuracy of the structures. Thus, the docking of high-resolution structures with small conformational changes yields an accurate prediction, while the docking of ultralow-resolution structures will give only the gross features of the complex. More information about the GRAMM methodology is on our laboratory research page.

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GRAMM was made publicly available following a number of requests from different labs. We would like to make it clear, however, that both the methodology and the program, at present, are in the process of active development, and have to be viewed like that. The program is free. However, we would expect proper references. Bug reports will be also appreciated. 

Temporary change:
We are currently in transition to the Center for Bioinformatics at the University of Kansas (to be completed in February). During that period, the registration form for GRAMM download will not be available. Please, go directly to the download area to get GRAMM.
To download GRAMM, please, fill in the registration form .

Platforms

GRAMM is compiled on SGI R10000, SGI R4000, SGI R4400, SGI R8000, Sun SPARC, IBM RS6000, DECAlpha, and PC (Windows and Linux). Windows version must work on all 32-bit flavors of the MS Windows operating system. Linux version was compiled on RedHat with glibc2.0.

Installation

1. Copy the executable file gramm to some standard location (e.g. /usr/local/bin on Unix) or to a separate directory (e.g., gramm103) and include the directory in the path.
2. Copy the data files (angXX.dat) to a separate directory (e.g., gramm103/dat). Define the environment variable GRAMMDAT with the name of this directory. How to define the environment variable:
• Unix C-shell (csh) or Tc-shell (tcsh): add the line setenv GRAMMDAT  directory-name to .cshrc file
• Unix Bourne shell (sh) and descendants (e.g. bash - standard shell on Linux, or Korn shell ksh): add the line export GRAMMDAT=directory-name to .profile file (or to .bashrc if using bash )
• If unsure what shell you are using, type echo $SHELL at the command prompt.
• After defining environment variable in Unix, 'source' your startup file or log into your account again. You can use echo $GRAMMDAT command to check the value of the variable.
• MS Windows 95, 98, Me: add SET GRAMMDAT=directory-name to your autoexec.bat file, then reboot (Windows Me will convert SET command into registry entry while rebooting and purge autoexec.bat after that - this is normal).
• MS Windows NT, 2000: use Environment tab in the System control panel Picture 1 ,  Picture 2 . If you are logged in as administrator, you will be able to add a  system-wide variable in the 'System Variables' section, otherwise use 'User Variables' section. First, select the proper section with a mouse, then type the new variable name and value in input lines at the bottom, and press Set button. After that, your new variable must appear in a list with other variables. On Windows XP the procedure is similar with the exception that the environment variables dialog is located at Control Panel -> System -> Advanced -> Environment Variables.
• To check the values of environment variables under MS Windows, open "MS DOS" prompt window and type SET command.
3. Copy the files rmol.gr, rpar.gr, wlist.gr to your working directory where you are planning to do the calculations. You will have to modify these files to define the task for GRAMM. If you are creating a shortcut in Windows to run GRAMM, you have to specify the working directory (start directory) in the shortcut properties and a parameter to pass to GRAMM when it is launched (e.g. gramm scan to dock or gramm coord to produce PDB output, see readme for details).
4. The README file is included both in PostScript and MS Word formats. The file describes parameter files and typical sets of parameter values used to run GRAMM.
5. NOTE: GRAMM takes as input molecular files in PDB format, and reads only the ATOM records from these files. In particular, HETATM records will be ignored.
6. When you run GRAMM, it will create a gramm.log file in the working directory. If something goes wrong, look for messages in gramm.log . The typical problems are:

ERROR: no parameters (scan,coord) for GRAMM	You have to run gramm scan or gramm coord , not just gramm
ERROR: ... step is too small for the max.(64x64x64) grid	Either your molecules are too large, or your grid step is too small. In either case, the size of 3D grid used internally by GRAMM for projections of molecules will exceed 64x64x64 elements. GRAMM will refuse to use grids larger than this limit, since the computation time becomes too large even on modern processors. You have to either increase grid step or cut your receptor into several smaller overlapping fragments using some molecular modeling software and dock those fragments separately with the ligand.
ERROR IN OPENING rpar.gr	Parameter files for your particular calculation (rpar.gr is one of them) must be present in your current working directory (i.e. the directory that is current when you issue the command gramm)
ERROR IN OPENING angXX.dat	Most likely, you did not properly define GRAMMDAT environment variable

• Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Aflalo, C., Vakser, I.A., 1992, Molecular surface recognition: Determination of geometric fit between proteins and their ligands by correlation techniques, Proc. Natl. Acad. Sci. USA, 89:2195-2199. (Basic algorithm of protein recognition by correlation technique with Fast Fourier transform; high-resolution geometric docking).

• Vakser, I.A., Aflalo, C., 1994, Hydrophobic docking: A proposed enhancement to molecular recognition techniques, Proteins , 20:320-329. (High-resolution hydrophobic docking).

• Vakser, I.A., Nikiforovich, G.V., 1995, Protein docking in the absence of detailed molecular structures, in: Methods in Protein StructureAnalysis (M. Z. Atassi & E. Appella, eds.), Plenum Press, New York, pp. 505-514.

• Vakser, I.A., 1995, Protein docking for low-resolution structures, Protein Eng., 8:371- 377. (Low-resolution protein docking).

• Vakser, I.A., 1996, Long-distance potentials: An approach to the multiple-minima problem in ligand-receptor interaction, Protein Eng., 9:37-41. (Interpretation of low-resolution docking in terms of energy potentials).

• Vakser, I.A., 1996, Low-resolution docking: Prediction of complexes for underdetermined structures, Biopolymers , 39:455-464. (Validation of low-resolution docking) .

• Vakser, I.A., 1996, Main-chain complementarity in protein-protein recognition, Protein Eng., 9:741-744. (Docking of C-alpha structures).

• Vakser, I.A., 1997, Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex, Proteins , Suppl.1:226-230. (GRAMM performance at CASP) .

• Vakser, I.A., Matar, O.G., Lam, C.F., 1999, A systematic study of low-resolution recognition in protein-protein complexes, Proc. Natl. Acad. Sci. USA, 96:8477-8482. (Large scale low-resolution docking).

Questions and comments to Ilya Vakser or Andrei Tovchigrechko