Grasp Enhancements





Grasp is one of the leading software packages for producing presentation and publication images of biomolecules. Pictures of molecular surfaces generated by Grasp are almost inevitable components of structural papers.

New Macros

Grasp is however widely regarded as a bit tricky to use. Fortunately, Grasp possesses a simple and effective macro language which can be used to automate common tasks. A few macros are distributed in the standard release and I have added several that I find useful to the default list.
The following macros are available:
 
  • Read a PDB file (also Alt-P on the keyboard)
  • Build a Molecular Surface (Alt-B)
  • Build a Solvent Accessible Surface (Alt-S)
  • Make a backbone worm (nicer than original version) (Alt-W)

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  • Atoms of charged residues coloured red (asp,glu) and blue (arg, lys, hip(=histidine+))
  • Atoms of hydrophobic residues coloured green (ala,leu,ile,val,trp,phe,gly,met,pro,cyx (=disulphide linked cys)
  • Atoms coloured by residue type (red,blue,green,gray=polar)
  • Atoms coloured by physical type (red=acceptor,blue=donor,green=apolar)

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  • Atoms coloured by occupancy
  • Atoms coloured by temperature factor
  • Surface coloured by occupancy
  • Surface coloured by temperature factor
    •  N.B. any values can be placed in the occupancy and temperature factor columns (e.g. degree of conservation) and consequently displayed on the surface or atoms

    To ensure that the occupancy and temperature factor columns are read the first two lines of the PDB file  should be

    GRASP PDB FILE
    FORMAT NUMBER=2
     
  • Electrostatic map on a protein's molecular surface generated using AMBER94 parameters
  • Electrostatic map on a biomolecular (i.e protein+DNA/RNA) surface generated using AMBER94 parameters
  • Electrostatic map on a protein's molecular surface generated using full charges
  • Electrostatic map on the protein's surface generated using full+backbone charges
  • Electrostatic map on a protein's solvent accessible surface generated using AMBER94 parameters
  • Electrostatic map on a biomolecular (i.e protein+DNA/RNA) SA surface generated using AMBER94 parameters
  • Electrostatic map on a protein's SA surface generated using full charges
  • Electrostatic map on a protein's SA surface generated using full+backbone charges
  • Electrostatic_Contours_at_+/-1_kt
  • Electrostatic_Contours_at_+/-3_kt

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  • Calculate total accessible surface area
  • Build and show cavities (but not accurately, see PRO_ACT for better results that can be imported to Grasp)

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    N.B. Many of the above functions require all hydogen atoms to be built into the structure for correct display.

    The AMBER94 potential

    The usual charges used with Grasp are called full.crg. They are quick to use with PDB files downloaded from the databank i.e. they don't give any error messages. However they suffer from an number of significant deficiencies. In particular, they are only suitable for proteins and even then omit charged histidines, charged termini and all the electrostatically important H-bonding groups.

    In order to obtain even semi-realistic electrostatic surfaces from Grasp it is necessary to use a set of charges which represent not only the fully charged chemical groups (eg. COO- on Asp, Glu) but the uneven charge distribution of all the groups that make up the biomolecule.

    The AMBER94 charge parameter set is widely used in molecular modelling and simulation and provides a much more complete picture of biomolecular electostatics. The charges have generally been derived by fitting to the results of fairly high level quantum mechanical calculations and, while not perfect, are fairly well regarded. The AMBER94 parameters include charges for all standard amino acid resides and both RNA and DNA (although with strange residue names). There are parameters to account for the altered electrostatics of terminal residues (with residue names NALA, CALA etc.), parameters for all the posible charge states of histidine (HIS (ND1 and NE2 deprotonated), HID (ND1 protonated), HIE (NE2 protonated), HIP (both protonated)), parameters for the uncharge forms of the usually charged groups (ASP->ASH, GLU->GLH,LYS->LYN), to account for situations of unusual pH or known to be shifted pKa and distinguishes free, disulphide linked and charged cysteine (CYS, CYX, CYM respectively). Parameters are also included for common ions but these are somewhat less rigourously derived and the effects of their presence on charge distribution of the binding groups from the biomolecule are not properly represented (still its better than having no ions).

    To use these parameters it is necessary to have a protein model which contains all of the necessary hydrogen atoms and has correct AMBER style residue names. The first is fairly easily acheived with CNS or Insight, the second with a text editor.
     

    Using these features

    To use these new parameters and macros UCL Biochemistry users should modify their .cshrc files to include

    setenv GRASP ~williams/grasp_data

    External users should download
    amber94_protein.crg
    amber94_nterm.crg
    amber94_cterm.crg
    amber94_dna.crg
    amber94_dnaterm.crg
    amber94_rna.crg
    amber94_rnaterm.crg
    amber94_ions.crg
    default.siz
    default_macros
    and place them in their own grasp_data directory.

    References

    A second generation force field for the simulation of proteins and nucleic acids Cornell, WD, Cieplak P, Bayly CI, Gould IR, Merz KM Jr, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW and Kollman PA. Journal of the American Chemical Society 117, 5179-5197 (1995).

    Useful links

    Queries, requests and donations of generally useful parameters or macros will be (mostly) happily recieved by Mark Williams
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