szmap

_images/szmap-howto.png

Semi-continuum Solvation

The szmap application analyzes sites near the surface of a protein or ligand using semi-continuum solvation theory, which combines a single explicit probe water with Poisson-Boltzmann continuum theory. By sampling various probe water orientations as it interacts with continuum solvent and with protein and ligand molecules, szmap can estimate thermodynamic properties useful in understanding the solvent role in ligand binding. One of the advantages of this semi-continuum approach is that szmap can place the probe anywhere one wishes to analyze, even locations that molecular dynamics simulations may not be able to sample adequately. The Technical Details section of chapter SZMAP Theory describes how these values are computed.

The most important question szmap can address is whether displacing water in a given region of a binding site is likely to increase or decrease binding affinity. A related question is what to replace a water with once the decision has been made to displace it. And finally, there is the question of whether water sites can be made to contribute to binding affinity without being displaced.

The analysis section of the Tutorial goes through how to determine whether a site is a good candidate for solvent replacement by looking at apo, complex and stabilization results. It also touches on questions of what to replace water with by looking at difference free energies, probe water orientations and gameplan results.

In addition to being run directly, szmap is called indirectly by gameplan. The szmap results are analyzed to produce hypotheses for ways to optimize the ligand, showing specific substituent geometries based on water energetics.

Running SZMAP

SZMAP Input and Output

szmap takes molecule files as input—usually molecules representing a protein and a corresponding ligand—and generates an OEBinary file as output. The molecular input is assumed to have explicit hydrogens and partial charges. Making sure the input molecules are properly prepared is essential in order to obtain useful results. See the Tutorial chapter for more information on preparing molecules.

When szmap reads input molecules, it checks for missing hydrogens and missing partial charges and will halt if the input does not appear to be complete. The option -warn_if_missing_hydrogens can be used to prevent halting, but before using it you should analyze the problem to see if it is due to an error in the input or something else, such as a disagreement with OEChem as to the proper bond order or charge state for your molecule. Mistakes in encoding alternate conformation codes can, for example, lead to very long and very short bonds, with the short ones interpreted as double bonds. And aromatic or double bonds that are not flat enough can cause OEChem to interpret them as single bonds. You may need to use a text editor or VIDA’s builder tool to resolve any pathologies you find, and then rerun pch.

szmap output contains the input molecules along with either one or more computed grids or with computed values attached to individual atoms. The output file can be opened in VIDA where the results will be displayed in the context of the input molecules. See the Tutorial and the chapters describing the WaterColor VIDA Extension, the Water Orientation VIDA Extension and the Color By Atom Properties VIDA Extension for step-by-step information on visualizing the results.

Calculations done at specific coordinates produce a tab-delimited table listing the results, which can be processed by Excel or other programs.

The output file can also be interpreted by the utility programs szmap_grid, grid_comp and szmap_report. Although VIDA is the best tool for analyzing szmap results, szmap_grid can be used to write out grid data in other formats.

Grid Calculations

_images/szmap-2w3a-apo-nddG.png

apo Neutral Difference Free Energy Grid

If a ligand is provided and no other selection criterion are specified, szmap will perform grid calculations centered around the ligand. If the structure has multiple binding sites, it is usually appropriate to focus on only one of these by making sure only one molecule is in the input ligand file. Other ways to define the calculation area include a bounding box, the region around a particular protein residue or small molecule, even the entire surface of the protein. Beware, surface calculations generate a very large number of points and take a correspondingly long time to compute. It is usually best to focus the computation on a smaller region.

> szmap -mpi_np 4 -stbl -prefix 1xyz_stbl -p 1xyz_prot.oeb.gz -l 1xyz_lig.oeb.gz

Because there are often a great many points to be tested in a grid calculation, the MPI multiprocessing options -mpi_np <num> and -mpi_hostfile <file> can be used to speed calculations by running szmap on multiple cores or multiple networked computers. There are some restrictions in using MPI—see chapter Installation and Platform Notes for more information.

_images/4std_stbl_mpi_speedup.png

Speed vs Processors

The figure Speed vs Processors is from a stabilization grid calculation run across a wide range of processor numbers. The dashed line is the diagonal for reference. With 8 processors, szmap runs over 6 times faster, and with 200 processors, about 150 times faster.

By default, grid output consists of four types:

  • neutral difference free energy, a hydrophilic/hydrophobic polarity scale described below,
  • van der Waals energy, an energy term not included in the neutral difference free energy,
  • order, the fractional loss of rotational entropy due to electrostatics, indicating how much energy can be liberated by displacing water at this site,
  • mask, an accurate solvent accessible surface—the region where the calculations were performed and the probe did not clash.

Neutral difference free energies compare the water probe with an uncharged or neutral water probe, a water where all the atoms have a partial charge of 0.0. The uncharged probe is a proxy for a hydrophobic group of the same size and shape as the standard probe water and these difference energies map out variations in the hydrophobic/hydrophilic nature of the binding site. High affinity ligands put nonpolar groups where these energies are positive and polar groups where these energies are negative, mimicking the donor-acceptor pattern of the solvent in the apo pocket.

Neutral difference free energies do not capture variations in van der Waals energies, which subtract out in the difference calculation. Van der Waals results are provided separately and complement the information in the neutral difference free energies.

Many additional grids are produced when the option -results_set max is specified. The most useful of these extra grids are probably psolv and wsolv—protein and water desolvation, respectively. They are always penalties (> 0.0 kcal/mol) and reveal the extent to which burying a charge costs energy, which needs to be compensated for by a complementary charge.

For most grid calculations, the -stabilization option is recommended. This causes complex, ligand and apo calculations all to be performed (although ligand calculations are by default restricted to solvent regions from the complex). Stabilization free energy values—computed as (complex + bulk) - (apo + ligand) where bulk-solvent is defined as 0.0—show how water energies are affected by binding. Negative stabilization free energies are regions that are stabilized by binding, or looked at another way, regions that stabilize binding. The simplest thing to do with them is leave them as they are, since they increase affinity. They can be displaced without destroying affinity, however, but only if they are displaced with a group that makes similar beneficial interactions. Positive stabilization free energies indicate regions where water is destabilized on binding. These waters lower affinity and are relatively easy to displace productively. Note that positive stabilization free energies can be found in regions where the neutral difference free energies in the complex are negative, and vice-versa. These two types of energies are not always correlated.

When comparing a series of ligands, all docked into the same binding site, the apo calculations can be done once separately by dropping the -stabilization option and specifying -apo_grids. Then these apo grids can be used in stabilization calculations for a series of ligands with the -use_apo_from option. If the ligands are all concatenated into one file, the -split_lig option will split each one out and perform the complex and ligand and stabilization calculations one-by-one.

> szmap -apo_grids -prefix 1xyz_apo -p 1xyz_prot.oeb.gz -l 1xyz_lig_series.oeb.gz
> szmap -mpi_hostfile myhosts.txt -stbl -use_apo_from 1xyz_apo.oeb.gz -split_lig  \
        -prefix 1xyz_stbl -p 1xyz_prot.oeb.gz -l 1xyz_lig_series.oeb.gz

Note

The line above with a ‘\’ as the very last character indicates that the command was too long to fit on one line and continues on the following line.

Most grids are masked to show only regions where the minimum Coulombic interaction + vdw energy is at or below -mask_cutoff (0.0 kcal/mol by default); anything above this is considered a CLASH. The mask_grid represents this solvent-accessible region. Somewhat surprisingly, errors in coordinates of atoms in a structure, even small errors, occasionally lead to clashes being indicated in areas where a crystallographic water is observed. Typically, there will be an adjacent region where the probe water does not clash.

Grid results can be processed with the utility grid_comp to break-out the region of the apo grid that has been displaced by the ligand.

> grid_comp -op lig_disp -i 4std_stbl.oeb.gz -o 4std_stbl_disp.oeb.gz

The volume of water displaced by the ligand plus the volume of water in the complex equals the volume of water in the full apo pocket. Displacement grids are useful in identifying, for example, precisely which waters are displaced by each of a series of substituents.

“At Coords” Calculations

_images/szmap-2z7k-coords.png

apo Neutral Difference Free Energy at Ligand Coordinates

When the -at_coords option is used, no grid is produced. Instead calculations are done only at the coordinates of any atoms in the coordinates file and written out attached to those atoms for use by szmap_report, the Water Orientation VIDA Extension and the Color By Atom Properties VIDA Extension. A tab-delimited table of these results is written to a text file, which can easily be loaded into a spreadsheet program for further analysis. “At coords” calculations produce many different results values at each point (see the Appendix), but the four types of results enumerated in the grid section above are the most useful.

> szmap -prefix 1xyz_coords -p 1xyz_prot.oeb.gz -at_coords 1xyz_lig.oeb.gz

szmap -at_coords calculations are much faster than grid calculations because they operate over a much more limited set of points. Keep in mind that a region where there is a large gradient in a property will be undersampled if the coordinates there are are widely spaced. Points labeled “CLASH” have Coulombic interaction + vdw energy greater than the -mask_cutoff (analogously to how the mask_grid is determined for a grid calculation). The “CLASH” label can be displayed in VIDA using the generic label function under the Aa+ button in the style panel.

If coordinates are taken from the ligand, as above, then stabilization calculations are not possible. But coordinates at other locations, such as crystallographic waters, can be used to rapidly produce stabilization results.

> szmap -stbl -at_coords 1xyz_waters.oeb.gz -prefix 1xyz_xtal_waters \
        -p 1xyz_prot.oeb.gz -l 1xyz_lig.oeb.gz

gameplan runs szmap at specific coordinates around the binding site and up-to two single bonds away from the ligand, analyzing the results to provide insight into ways to optimize the ligand.

Probe Orientation Data

_images/szmap-2z7k-orient.png

Probe Water Orientations

In both types of szmap results, grids and “at coords”, information is stored about the energies and probabilities of the probe for each point. This information can be processed by the Water Orientation VIDA Extension to identify regions of local energy minima and maxima and to display probe order or disorder. The probe geometry at dominant sites in the region where water is displaced can be compared to that of the ligand. High affinity ligands mimic both the difference free energy pattern and the specific geometry of the displaced water. This more “molecular” display is often easier to understand than continuous grids of data and it contains structural information that complements the numerical energy values.

Command Line Interface

A description of the command line interface can be obtained by executing szmap with no arguments.

prompt> szmap

will generate output similar to the following:

          :jGf:
        :jGDDDDf:                SS    ZZZZZZ  M     M     A     PPPPP
      ,fDDDGjLDDDf,            SS  SS      Z   MM   MM    A A    P    P
    ,fDDLt:   :iLDDL;          S          Z    M M M M   A   A   P    P
  ;fDLt:         :tfDG;          SS      Z     M  M  M   AAAAA   PPPPP
,jft:   ,ijfffji,   :iff            S   Z      M     M  A     A  P
     .jGDDDDDDDDDGt.           SS  SS  Z       M     M  A     A  P
    ;GDDGt:''':tDDDG,            SS   ZZZZZZ   M     M  A     A  P
   .DDDG:       :GDDG.
   ;DDDj         tDDDi         Copyright (c) 2009-2015
   ,DDDf         fDDD,         OpenEye Scientific Software, Inc.
    LDDDt.     .fDDDj          Version: 1.2.1
    .tDDDDfjtjfDDDGt           Release: 20150305
      :ifGDDDDDGfi.            OEChem version: 1.9.2 20150305
          .:::.                Platform: redhat-RHEL5-g++4.1-x64
  ......................
  DDDDDDDDDDDDDDDDDDDDDD
  DDDDDDDDDDDDDDDDDDDDDD

  Licensed for the exclusive use of Company Name.
  Licensed for use only in Site.
  License expires on August 15, 2015.

To cite please use the following:
  SZMAP, version 1.2.1, OpenEye Scientific Software, Inc.,
  Santa Fe, NM, USA, www.eyesopen.com, 2015.


No arguments specified on the command line
<path>/szmap : calculate solvent thermodynamic parameters
Required parameters:
    -protein : Input protein file.
For more help type:
  <path>/szmap --help

Required Parameters

-protein <filename>
-p <filename>

[keyless parameter 1]

The format must be one that retains partial charges: OEBinary, Tripos .mol2, or DelPhi flavor PDB (where there is radii in the occupancy field and charge in the B-factor field).

The file format of the input file is automatically determined from the file extension. The extensions .oeb, .oeb.gz can be OEBinary; .mol2 for Tripos Mol2 files; .pdb for PDB format files.

File type Extension
OEBinary .oeb .oeb.gz
PDB(DelPhi) .pdb .ent .pdb.gz .ent.gz
MOL2 .mol2 .mol2.gz

Warning

By default, charges and radii are expected to be in this file and the results will be meaningless if they are missing. The program pch is provided to add charges.

Atoms from waters, metals, ligands, co-factors, modified proteins and nucleic acids will be included in the calculation. VIDA can be used to create a new molecule where the protein is split from these.

Command Line Options

Input File Options

-ligand <filename>
-l <filename>

[keyless parameter 2]

The format must be one that retains partial charges: OEBinary, Tripos .mol2, or DelPhi flavor PDB (where there is radii in the occupancy field and charge in the B-factor field).

The file format of the input file is automatically determined from the file extension. The extensions .oeb, .oeb.gz can be OEBinary; .mol2 for Tripos Mol2 files; .pdb for PDB format files.

File type Extension
OEBinary .oeb .oeb.gz
PDB(DelPhi) .pdb .ent .pdb.gz .ent.gz
MOL2 .mol2 .mol2.gz

Warning

By default, charges and radii are expected to be in this file and the results will be meaningless if they are missing. The program pch is provided to add charges.

-warn_if_missing_hydrogens
If specified, missing hydrogens will not terminate the program, but will instead generate a warning message. Otherwise, missing hydrogens on the ligand or on more than 10 percent of the protein heavy atoms will cause szmap to fail.
-split_lig
Separate ligand file into individual molecules and run each individually.

Output File Options

-prefix <prefix>

Prefix used to name output files. Using -prefix FOO will create results in an OEBinary file named FOO.oeb.gz (see -output_mol). The table produced with -at_coords will be written to FOO.txt (see -table). Additionally, a parameter file named FOO.param (see -param) and a log file named FOO.log (see -log).

[default = szmap]

-output_mol <filename>
-o <filename>

[keyless parameter 3]

OEBinary output file (.oeb or .oeb.gz), with calculated results attached to a copy of the input -protein and any -ligand.

If not specified, -prefix will be used to name the output.

-table <filename>
A tab-delimited table of results from -at_coords calculations is written to this file. If specified, this will override the filename created from -prefix. Specify -table - to send to standard-output.
-std_box <filename>

Write standard (complex) grid bounding box to output ‘box molecule’ coordinate file.

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

To facilitate visualization, box corners are represented by nitrogen atoms and bonds define the box edges in formats that support bonds. Use -box_mol to select based on this file.

-lig_box <filename>

Write ligand grid bounding box to output ‘box molecule’ coordinate file.

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

To facilitate visualization, box corners are represented by nitrogen atoms and bonds define the box edges in formats that support bonds. Use -box_mol to select based on this file.

-apo_box <filename>

Write apo grid bounding box to output ‘box molecule’ coordinate file.

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

To facilitate visualization, box corners are represented by nitrogen atoms and bonds define the box edges in formats that support bonds. Use -box_mol to select based on this file.

Selection Options

If a -ligand is provided but none of the selection method’s options are specified, points are selected around the ligand when grids are generated, even for apo grids (see -distance_cutoff).

-at_coords <filename>
-coords <filename>

Perform calculations just at the coordinates of atoms in any molecules in the file. Write those molecules, with the (masked) results attached to the atoms, to the output file.

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

Text formats such as .xyz are easily modified in a text editor to specify an arbitrary set of coordinates.

The tags that will be used when assigning values to atoms are listed in Appendix 2: SZMAP Atom Properties.

A tab-delimited table of calculation results is printed to a text file (see -table). In the abbreviated column heading, n_ stands for neutral and v_ stands for vacuum. A mask value of 0 indicates that the intvdw value is above -mask_cutoff and this row of data should not be used.

-residue_number <number>
-res <number>
Select grid points around the selected residue (see -distance_cutoff).
-residue_chain <letter>
-chain <letter>

Protein chain used with -residue_number. Case sensitive. Underscore (‘_’) stands for blank.

[default = ‘_’]

-residue_insert <letter>
-inscode <letter>

Protein insertion code used with -residue_number. Case sensitive. Underscore (‘_’) stands for blank.

[default = ‘_’]

-like_std <filename>
Select points in the same bounding box as the standard (complex) grids from the specified OEBinary (.oeb or .oeb.gz) file.
-like_lig <filename>
Select points in the same bounding box as the ligand grids from the specified OEBinary (.oeb or .oeb.gz) file.
-like_apo <filename>
Select points in the same bounding box as the apo grids from the specified OEBinary (.oeb or .oeb.gz) file.
-like_box <filename>
Select points in the same bounding box as the box_mol in the specified OEBinary (.oeb or .oeb.gz) file.
-around_mol <filename>
-around <filename>

Select points enclosing the atoms in the specified file (using -distance_cutoff to define how much extra space beyond the atoms is include).

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

Text formats such as .xyz are easily modified in a text editor to adjust the region of interest.

-box_mol <filename>

Select points in bounding box defined by atoms in the input ‘box molecule’ file (withthout a -distance_cutoff).

File type Extension
OEBinary .oeb .oeb.gz
MacroModel .mmod .mmod.gz
MDL .mdl .mdl.gz
MOL2 .mol2 .mol2.gz
MOPAC .mopac .mopac.gz
PDB .pdb .ent .pdb.gz .ent.gz
SDF .sdf .mol .sdf.gz .mol.gz
XMol xyz .xyz .xyz.gz

Text formats such as .xyz are easily modified in a text editor to adjust the region of interest.

-bounding_box <xmin> <ymin> <zmin> <xmax> <ymax> <zmax>
-bbox <xmin> <ymin> <zmin> <xmax> <ymax> <zmax>
Select points in the bounding box defined by minimum and maximum coordinate values.
-surface_points
-surf

Select grid points over the entire surface of the input molecule(s).

Warning

This usually results in very long run times.

-distance_cutoff <number>
-dcutoff <number>

Maximum distance from atoms of selected points, a margin around the focus region.

[default = 6.0 Å]

-value_cutoff <number>
-vcutoff <number>

Minimum FRED surface shape score value for selected points.

[default = 0.05]

-restrict_calc <level>

Control which points are used for calculations. Restricting calculations makes szmap run faster but make the that portion of the results less useful. In particular, restricting apo calculations may not be worth the speed increase because it prevents you from being able to analyze the full apo pocket.

Level Meaning
none Calculate full grids
ligand Restrict ligand calc to region from complex
apo Restrict apo calc to region from complex
both Restrict ligand & apo to region from complex

[default = ligand]

Grid/Coord Options

If a grid or coord request option is not specified, all apo results will be generated, and if a ligand is supplied, all std (complex) results as well.

-results_set <type>
-properties <type>
-grids <type>

Defines which sets of properties are included in grid or coordinate results.

Type Output
min Only the standard (complex) results; minimal grid output; full coord output
default Both standard and apo results, if possible; minimal grid output; full coord output
max Both standard and apo results, if possible; Full grid and coord output

min or default used for a grid calculation produces the following properties:

  • neut_diff_free_energy_grid (or the corresponding lig or apo grid)
  • vdw_grid
  • order_grid
  • mask_grid

See Appendix for lists of properties.

[default = default]

-stabilization
-stbl
Generate (complex - (ligand + apo-pocket)) values that show where water is stabilized or destabilized upon ligand binding. This requires extra calculations with the ligand alone.
-mask_cutoff <number>

Points where the minimum interaction + van der Waals energy above this cutoff will be set to 0.0 in the output grids.

[default = 0.0 kcal/mol]

-grid_spacing <number>
-space <number>

Distance between grid points. We recommend this value be above 0.25 Å. szmap creates a grid by first building a temporary grid around the protein and/or ligand molecules that contains values of a function describing the space near the molecular surface. This temporary grid has the same grid spacing as the final grid, so using a very fine grid spacing can generate enormous temporary grids that fill memory.

[default = 0.5 Å]

-standard_grids
-std_grids
-cplx_grids
-std_coords
Generate all standard (holo-complex) grids or coords. The actual grids or coord data will depend on -results_set.
-lig_grids
-lig_coords

Generate all ligand grids or coords. The actual grids or coord data will depend on -results_set.

The std and/or apo grids will still be generated as usual even if this option is specified.

-apo_grids
-apo_coords
Generate all apo grids or coords. The actual grids or coord data will depend on -results_set.
-point_grid
Generate the grid of test points where the calculation is done (1 = test, 0 otherwise). If a ligand is provided, values are for the protein/ligand complex.
-lig_point_grid
Generate the grid of test points where the calculation is done (1 = test, 0 otherwise). Values are for the ligand without the protein.
-apo_point_grid
Generate the grid of test points where the calculation is done (1 = test, 0 otherwise). If a ligand is provided, values are for the protein without the ligand.

Calculation Options

-num_orientations <number>
-rot <number>

Number of probe-molecule orientations to sample at each grid point. If this number is set to 24, 60, 216, 360, or 648 then the set of rotations will be symmetric. Otherwise, they will be random and may have lopsided gaps in coverage. For most purposes, 60 is the minimum required for reliable energy calculations and 360 generates robust results.

[default = 60]

-dielectric_model <type>
-model <type>

Type of surface defining the boundary between -inner_dielectric and -outer_dielectric values.

Type Meaning
gaussian Dielectric value changes smoothly over a distance of approximately 2 Å.
molecular Dielectric changes abruptly at molecular surface

[default = gaussian]

-inner_dielectric <number>
-eps_in <number>

Dielectric value used inside the protein and ligand atom surface (see -dielectric_model).

[default = 1.0]

-outer_dielectric <number>
-eps_out <number>

Dielectric value used outside the protein and ligand atom surface (see -dielectric_model). This is the dielectric of bulk solvent.

[default = 80.0]

-salt_conc <number>
-salt <number>

Salt concentration in Poisson Boltzmann calculation (units: moles/liter).

[default = 0.05 M]

-zap_spacing <number>

Distance between grid points within the ZAP calculation. To avoid excessive memory requirements and ensure stability during the PB calculation, it is usually best for ZAP spacing to be greater than 0.25 Å.

[default = 0.5 Å]

-boundary_spacing <number>
-boundary <number>

Extra buffer outside the extents of the selection molecule.

[default = 4.0 Å]

-boundary_radius <number>

Size of probe for boundary calculation.

[default = 1.4 Å]

-water_charge <type>

Which charges are used on the probe water: scaled or am1bcc. Scaled means scale AM1BCC charges to match the water dipole.

[default = scaled]

-vdw_scale <number>

Scale for van der Waals between probe atoms and other atoms.

[default = 1.0]

-use_apo_from <filename>

Use the apo grids in the .oeb results file from a previous szmap run rather than calculating them. This can speed up calculations for a series of ligands docked to a single ligand.

This option is also useful when the apo protein and the complex adopt slightly different states. For example, a key amino acid may have an ionized sidechain in the apo protein and a neutral sidechain in the complex.

MPI Options

These options control how MPI is used. Unless one of these options is specified, szmap will run in single processor mode. See chapter Installation and Platform Notes for more information, including the format of the host file.

-mpi_np <number>
Run szmap calculations in MPI miltiprocessor mode using the specified number of processors. If an MPI hostfile is not specified with the -mpi_hostfile option all processor will be launched on the local machine.
-mpi_hostfile <filename>

Run szmap calculations in MPI miltihost mode using the specified MPI hostfile. If an MPI hostfile is not specified all processes will be run on the local machine. The hostfile format is a text file with each line specifying a machine and the number of processes to launch on it.

The following example hostfile specified 3 hosts that can run up to 4, 2 and 5 processes respecitively.

host1.mydomain.com slots=4
host2.mydomain.com slots=2
host3.mydomain.com slots=5

This example hostfile would typically be used with -mpi_np 11 to make use of all the processors (4+2+5=11).

Note that multiprocessor is only supported on the local machine under Windows, and in homogeneous enviroments for other architectures (i.e., machines with the same operating system enviroment).

Other Options

-param <filename>
Defines the control parameter file. This file can contain a collection of parameters which can be used instead of writing each parameter to the command-line. In addition, the parameter file written by any szmap run (see -prefix) can be used with the -param flag in subsequent szmap runs. Any command given explicitly on the command line will supersede any command found in a file specified with the -param flag.
-logfile <filename>
-log <filename>
If specified, this will override the filename created from -prefix. Specify “-log - ” (dash) to send to standard-output.
-progress <style>

How to display progress information:

Style Output
none no progress shown
dots print a period (.) for every point tested
percent print percentage complete every 10 points
log print percentage to log file

[default = percent]

-verbose
-v
Print additional information to log during calculations.