Molegro virtual docker manual

Various constraints makes it possible to alter the energy landscape e. Constraints can be defined based on chemical properties e.

In MVD, sidechain flexibility is implemented by softening the potential during the docking by increasing the tolerance of the PLP-potentials or by weakening selected sidechains interactions , docking a diverse set of poses, and finally optimizing the sidechain configurations. It is also possible to manually minimize a receptor structure. After the docking simulation has completed, the found poses can be inspected simultaneously with their matching receptor conformation directly in the pose organizer.

MVD makes it possible to dock ligands against docking templates. Similar to pharmacophores, templates are build from relevant chemical properties like charge and hydrogen bonding capabilities and can be auto-generated from one or more ligand conformations. Templates can be used in several ways:. Please see the user manual for a more thorough explanation of Molegro Virtual Docker features. Molecule Import and Preparation It is easy to import and prepare molecules.

Parsing warnings and errors are shown in a convenient hierarchy. MVD detects bonds, aromaticity, assigns charges, and adds explicit hydrogens. Various steps in running the Docking Wizard. The reason for this is, that if you for example want to reward ligands with a hydrogen acceptor close to hydrogen donor in the protein, it does not make sense to punish other atoms in the vicinity of the constraint if one hydrogen acceptor is already at its optimal distance from the donor.

It is used to constrain a specific ligand. Since Ligand Atom Constraints are defined using a list of atom IDs, they are specific to ligands and are only applied to the ligand on which they are defined. To create a Ligand Atom Constraint, select a number of atoms in the same ligand in the Visualization Window. Ensure that no other objects are selected, and choose Constraint Selected Ligand Atoms from the context menu right-click mouse button.

It is also possible to use the context menu on a single ligand atom Create Ligand Atom Constraint without performing a selection. The Ligand Atom Constraint dialog will appear see Figure It is possible to modify the list of atoms in the ligand by entering a comma-separated list of IDs.

It is possible to choose whether the chosen atoms in the ligand should be rewarded or penalized for contacts with the target molecules proteins, cofactors and water. The criteria for contact used here is purely based on the distance between the chosen ligand atoms and the closest atom in any target molecule.

Figure Ligand Atom Constraint dialog. Typical Uses Constraints are useful if something about the system is known in advance. If perhaps a hydrogen bond from a hydrogen donor was known to be present — a distance constraint could be set up at the position of the protein hydrogen donor, and a hard constraint could force hydrogen acceptors in the ligand to satisfy the hydrogen bond. A shortcut is provided by clicking on the docking icon gear wheel on the tool bar.

Additionally, the keyboard shortcut F1 is available. Notice: In order to initiate the docking, at least one protein and one ligand molecule have to be present in the workspace. Figure Select which ligands to dock. If more than one ligand is available the user can select which ones to use by clicking on the corresponding molecules in the window.

If more than one ligand is selected, all selected ligands will be docked one at a time. Structural waters and cofactors if any are always included in the docking simulation remember to remove them from the workspace if they should not be included.

Moreover, a reference ligand can be specified at the bottom. The reference ligand is used to calculate the root-mean-squared deviation RMSD between the reference ligand and the docked pose. The reference ligand - or ligands - are only available if they are compatible w.

Notice: If more than 10 ligands are present in the workspace, a subset of the ligands can be selected for docking using the Specify ligand range option not shown on Figure The grid-based scoring function provides a times speed up by precalculating potential-energy values on an evenly spaced cubic grid see Appendix:Appendix XII: MolDock Score [Grid] for more details. Figure Choosing scoring function. The Ignore distant atoms option is used to ignore atoms far away from the binding site. Thus, atoms more than Radius angstroms away from the center of the binding site are ignored in the scoring function.

This reduces the overall computing time significantly when working on large molecules. Notice that charged atoms capable of long-range interactions are always taken into account in the scoring function.

The Enforce hydrogen bond directionality option is used to check if bonding between potential hydrogen bond donors and acceptors can occur. If hydrogen bonding is possible, the hydrogen bond energy contribution to the docking score is assigned a penalty based on the deviations from the ideal bonding angle. Using this option can significantly reduce the number of unlikely hydrogen bonds reported.

For the grid-based scoring function, the Grid resolution option not shown in Figure 45 can be used to set the granularity of the generated energy grids.

The Origin determines which area of the protein is expected to include the binding site. If cavities have been identified the user can pick one of these as the preferred area of interest. Further, if a reference ligand is being used, the center of the reference ligand can be used.

By default if no cavities have been identified and no reference ligand is specified , the center of the bounding box spanning all protein s will be used.

The actual center of the binding site used is listed in the X, Y, and Z boxes in the window. Besides the center of the binding site, a Radius can be specified default is 15 angstrom.

Notice: A sphere in the Visualizer Window indicates the position and size of the current search space region see Figure Figure Example of search space region green sphere. Enable or Disable Additional Constraints If constraints besides the search space region have been added to the workspace, they can be toggled on and off in the Enable or Disable Additional Constraints tab see Figure In order for a constraint to be meaningful it must be defined within the current search space region.

From MVD v1. This is usually the case when the ligand has lots of internal degrees of freedom many torsion angles. Notice: MolDock SE is still experimental, as all parameters has not been finetuned yet. Although it should be stable, it is still to be considered a technology preview version. The Number of runs specifies the number of times that the docking simulation is repeated for each ligand chosen to be docked.

Sometimes more than one run is needed to identify promising poses in particular for ligands having more than 15 flexible torsions or if no promising cavities exist. If cavities have been identified see Section 5.

This option greatly reduces the overall docking process and increases the accuracy of the docking procedure.

However, if the ligand does not bind in the region specified by the selected cavity, this option should be disabled. If randomization of orientation is not enabled, the docking search algorithm will be biased towards the orientation of the input ligand to be docked see Chapter 8 for more details. Notice: For large ligands with more than flexible bonds, runs are sometimes needed.

Using the MolDock SE search algorithm and the grid-based version of the docking scoring function can reduce the computational load significantly good results have been reported using this combination and setting the Number if runs to The General Settings show the parameters used by the search algorithm.

The default values shown are generally suitable for most docking tasks. However, in some cases increasing the Population size to can improve the performance of the docking procedure.

Figure Customizing the search algorithm. Pose Clustering Instead of returning only one final pose for each docking run, it is possible to return multiple poses representing different potential binding modes.

This can be useful when the best-scoring i. Poses found during the docking run will be clustered put into bins using the RMSD criteria.

Only the lowestenergy representative from each cluster will be returned when the docking run is completed. All poses returned from the runs will be clustered and similar poses are removed keeping the best-scoring one. Depending on the RMSD threshold specified, more or less diverse poses combined for all the runs will be reported. Figure Pose clustering options.

Notice: The actual number of poses returned may be lower than the maximum number of poses specified in Max number of poses returned. However, the overall best-scoring pose will always be returned. Errors and Warnings Figure Any warnings or errors are shown on the last page in the wizard. The Docking Wizard reports errors and warnings found, such as non-bonding atoms in molecules, steric clashes between atoms, unsupported residues, missing hydrogens in proteins, etc.

A detailed description of each warning and error is shown at the bottom of the Errors and Warnings tab see Figure Setup Docking Execution In the final tab see Figure 53 , two choices are available for executing the docking simulation. Run docking in separate process is the default choice, which creates a MVD script that is executed in an external process Chapter 10 describes the MVD Scripting Interface in more details.

A copy of the current workspace is used, so the user can continue working with the current workspace without interfering with the docking simulation e. The second choice Create a docking script job, but do not run it now creates a docking script using the currently selected parameter settings. The Output directory specifies where the docking data MVD script file, MVD script log file, docking results file, and found poses will be stored.

The MVD script file script. Details about the poses returned after the docking simulation e. The mvdresults file is used by the Pose Organizer to show detailed information about the poses and to dynamically load the molecular structure of the poses see Section 6. Finally, each pose is stored in SDF format. These files are used by the Pose Organizer to show the 3D conformations of the poses in the Visualization Window.

Finally, when the Start button is pressed, the docking run will start and the Molegro Virtual Docker Batchjob dialog will pop up - showing the current status and progress of the docking see Figures 52 and The blue graph shows the energy of the best pose and the red graph shows the mean energy of the entire population of candidate solutions see Appendix II: Docking Search Algorithm for more details about the docking simulation and the population terminology.

It allows you to browse the list of current poses, to see detailed information about specific energy contributions, to visualize hydrogen bonds, electrostatic interactions, and to calculate ranking scores and estimate binding affinity energies. The Pose Organizer can be invoked in several ways. Otherwise it can be invoked by using the context menu on the Poses category in the Workspace Explorer or using Docking Pose Organizer if poses are present in the Workspace Explorer.

When the Pose Organizer is invoked it displays a list of poses parsed from the mvdresults file or poses currently in the workspace. The table in the middle of the dialog window shows various columns with information about different energy contributions and other data for each pose. The columns can be changed under the Settings tab pane. A panel in the bottom of the dialog Sorting Criteria allows the user to sort the table by up to three different criteria.

By default the table in the middle supports multiple selection, i. This setting is useful for quick comparison of different poses. This default behavior can be changed by selecting Dynamic update notice: disables multiple poses selection. In this mode only one pose is shown at a time. In return it offers the possibility to visualize different interactions for the current selected pose e. When inspecting poses obtained from different ligands, the Only show top The selection of the top poses are based on the currently chosen Sorting criteria.

Figure The Pose Organizer dialog. Notice: A detailed energy analysis is available by right-clicking poses in the table and selecting Show Detailed Energy Analysis.

Additional options are available in the context menu allowing the user to select, remove, and export poses. These options are also available from the File and Edit menus located in the Pose Organizer dialog.

Figure Pose Organizer settings. It allows you to visualize hydrogen bonds, electrostatic interactions, orient hydrogens in the protein and ligand to their optimal position, and dynamically show residues close to the chosen pose. The Orient hydrogens to optimal position option is useful when inspecting poses as this makes it easier to see if the hydrogen bond is optimal. These scoring function values are already calculated if the poses are imported from a mvdresults file.

Pressing the Recalculate Energies button will recalculate the scores for each of the three measures using the coefficients specified in the files for the binding affinity and re-ranking scores. The ranking score function is computationally more expensive than the scoring function used during the docking simulation but it is generally better than the docking score function at determining the best pose among several poses originating from the same ligand.

The pKi is predicted using a combination of energy terms and molecular descriptors and then converted to a binding affinity estimate using the equation above. The coefficients for the binding affinity terms were derived using multiple linear regression.

The pKi estimator has been calibrated using a data set of more than complexes with known binding affinities. The correlation coefficient was 0. In general, estimating the binding affinity is a difficult task. Although the accuracy of our binding affinity estimation is on par with other approaches, our current implementation is considered a work in progress and we expect to improve it further.

The Table Columns Panel The bottom panel Table columns determines which columns descriptors that are shown in the table on the first tab. Table 1 describes the descriptors that are available. To save a workspace, select File Save Workspace As Alternatively, use the keyboard shortcut Ctrl-S. Notice: Visualization objects surfaces, labels, cavities, interactions, Exporting Molecules The Export Molecules dialog can be used to export all or a selection of the molecules available in the workspace see Figure Figure Export Molecules dialog: Select which molecules to export.

To export molecules, select File Export Molecules When invoking the Pose Modifier, a new pose is created. Figure Pose Modifier dialog. Notice: It is not possible to directly modify poses after the workspace has been saved and reloaded. However, ligands can be modified any time. To modify poses saved, these can be converted to ligands and modified afterwards which will result in a new modified pose. Different interactions can also be visualized on-the-fly Dynamic Update tab.

The Copy to Clipboard button can be used to copy the table to the clipboard for further inspection in an external text editor or spreadsheet. By selecting three atoms in one ligand, and selecting three atoms in another ligand, a new context menu appears when clicking on an atom in one of the molecules - Align This will align the molecules.

The atoms are aligned in the same order as they are selected, that is, the first selected atom in ligand 1 is aligned to the first selected atom in ligand 2 etc. Therefore, it is important to ensure that the selection order is correct and that no other atoms are selected.

Alignments can be undone click the undo button in the tool bar. Notice: Only alignments with three selected atoms in each molecule are possible. Preference settings are categorized in General, Graphics, and Debug tabs. Figure First tab of the preferences dialog. Modern computers with dedicated 3D hardware should be able to run at highest quality even when rendering relatively large molecules.

It is easy to test new quality settings by selecting the level of quality and pressing the Apply button. Figure The graphics tab of the Preferences dialog. The final settings tab, Debug, contains various options that can be used to provide additional debug information. For standard uses, it is not recommended to change the default settings of any of these options.

The Create system log in 'Logs' directory option is used to toggle whether a system log is created for each execution of MVD. The system log contains information of user actions conducted and is used to track potential bugs and performance problems. The log files are stored within the Logs directory located in the same directory as the mvd executable file. Notice: If you encounter problems with MVD please email the log file created before the crash to: [email protected] 7.

If more than one file is listed separated by spaces , each file will be imported. Python to interact with MVD and control the docking process. See Chapter 10 for more details. Finally, the -currentPath parameter can be used to override the working directory specified in the general preference settings with the current path. This is particularly useful when running MVD from different working directories using a terminal window or when using a script to start up MVD.

Remember to backup the original file before modifying the coefficients. By taking the following suggestions into account, we hope that common pitfalls can be avoided. It is therefore advisable to manually inspect the molecules in particular ligands and check bond orders, hybridization states, and if hydrogens are correctly assigned.

The complexity of the docking search can be significantly reduced, if the number of torsions that are set flexible during the docking run is lowered. Bonds can be set rigid during docking using the context menu right-click on the bond and select Set Flexibility Rigid while docking.

However, for large proteins or proteins having a lot of cavities, it is sometimes necessary to increase the number of cavities reported Max number of cavities.

Also remember to set the binding site Origin in the Docking Wizard to the specific cavity being investigated. For instance, knowledge about preferred binding mode or ligand conformation can be used to set constraints or reduce the search space covered e. Constraints and binding site settings in the Docking Wizard. The current root atom can be visually identified if visualization of root-atoms is enabled see Section 7. The root atom is used as root in the torsion tree that is constructed when docking flexible ligands.

Docking performance may be improved by setting the root atom in a region of the ligand that is suspected to contribute significantly to the docking energy.

Before starting the docking run, potential cavities should be identified see Section 5. Found cavities can be used to specify the origin of the search space in the Docking Wizard and constrain candidate solutions to the region covered by the cavity by enabling the Constrain poses to cavity option in the Docking Wizard.

However, the Radius should be set as small as possible to make the docking search efficient. Likewise, the Origin center of the search space region can be manually adjusted to focus the sampling of candidate solutions to a specific region. This is particularly important if the cavity volume is much bigger than the ligand for large cavities, focusing on one specific part of the cavity will significantly increase the docking accuracy.

However, in some cases e. Typically, about runs are needed to ensure convergence to the lowest-energy solution. For large ligands with more than flexible bonds, runs are sometimes needed. When conducting more than one docking run, Randomize ligand orientation should be enabled see Biased Orientation bullet below.

Additionally, it is recommended to ignore similar poses returned see Section 5. It is important to inspect the warning messages and see if further actions are needed. Otherwise, the docking run might be unsuccessful. If randomization of orientation is not enabled, the docking search algorithm will be biased towards the orientation of the input ligand to be docked.

Notice: Using the biased orientation can be advantageous if the orientation of the ligand to be docked is known beforehand or if the orientation is somewhat similar to the input structure. For instance, if another inhibitor is known, it can be used to align the ligand to the inhibitor before the docking run is started see Section 6. In these cases, a biased orientation will allow the docking search algorithm to focus more on that specific orientation or nearby orientations leading to more accurate docking results.

Ideally, the highest-scoring pose should represent the best-found binding mode. However, this is not always the case. A useful feature is to evaluate the poses using either the Ranking Score or the Binding Affinity estimate.

The Ranking Score makes use of a more advanced scoring scheme than the docking scoring function used during the docking run. Using the Ranking Score will often increase the accuracy of the ranked order of the poses. It is also possible to perform a full-text search by choosing the Search tab from the sidebar.

Figure 'Tip of the Day' dialog. The dialog can be manually invoked from the Help menu or automatically shown on startup. The automatic startup setting can be toggled in the dialog or from the general Preferences dialog. Please visit www. To obtain additional support send an email to [email protected] molegro virtual docker — user manual 10 Script Interface The Docking Wizard guides the user through the different settings for the simulation, and then creates a small script file which contains instructions on how the docking should proceed.

The default behavior for the Docking Wizard is then to spawn a script interpreter in another process — the script interpreter and the main application runs completely separated and execute the script. However greater flexibility is possible by writing custom scripts: for instance this makes it possible to dock a number of ligands against several distinct targets. It is also possible to split large docking runs into several scripts and run them on different machines. Notice: A MVD script job basically runs in a single thread.

However by splitting the job into two or more jobs and running them concurrently all available CPU's can be utilized. Otherwise, the script file will not be recognized and parsed by MVD. It is also possible to start a script job with no graphical user interface without the script parsing progress dialog.

This can done by using the -nogui command line argument: Example: mvd docktest. Otherwise the system might kill the process when the user logs off because the X11 server might be shutdown. A complete list of commands can be found in Appendix X: Script Commands. In this mode the MVD application starts and waits for user input from the command line i. To start MVD in interactive mode, use the following syntax: Example: mvd -interactive The purpose of the interactive mode is to allow scripting languages capable of writing to and from the standard input and output of a program to control the docking process.

This can be useful for automating larger docking runs. The wrapper spawns a new MVD process when the object is instantiated and runs MVD in interactive mode to pass commands to it. The process can be terminated by calling exit on it. In order to use the wrapper, copy the MvdWrapper. Also notice that in order to communicate through pipes with the MVD application be sure to instantiate with a reference to the 'MVDConsole.

The MolDock scoring function further improves these scoring functions with a new hydrogen bonding term and new charge schemes. The EPLP term is a piecewise linear potential described below. The second term describes the electrostatic interactions between charged atoms. The numerical value of To ensure that no energy contribution can be higher than the clash penalty the electrostatic energy is cut-off at the level corresponding to a distance of 2.

The charges are set according to the scheme listed in Table 2. Zn, Ca, Fe. A bond is considered a hydrogen bond if one of the atoms can donate a hydrogen atom and the other atom can accept it. The atom types are assigned according to the scheme shown in Table 4. The PLP hydrogen bond term mentioned above only depends on the distance between atoms. If it is not possible to calculate one of these factors it is omitted. This is for example the case for hydroxyl rotors where the exact location of the hydrogen is not investigated during docking, and the two first factors cannot be calculated.

The second term is a torsional energy term, parameterized according to the hybridization types of the bonded atoms see Table 5. Notice that this angle is not necessarily uniquely determined. The average of the torsional energy bond contribution was used if several torsions could be determined.

Thus, Eclash term punishes infeasible ligand conformations. Evolutionary algorithms EAs are iterative optimization techniques inspired by Darwinian evolution theory.

In EAs, the evolutionary process is simplified and thus it has very little in common with real world evolution. Nevertheless, during the last fifty years EAs have proved their worth as powerful optimization techniques that can assist or replace traditional techniques when these fail or are inadequate for the task to be solved. Basically, an EA consists of a population of individuals candidate solutions , which is exposed to random variation by means of variation operators, such as mutation and recombination.

The individual being altered is often referred to as the parent and the resulting solution after modification is called the offspring. Sometimes more than one parent is used to create the offspring by recombination of solutions, which is also referred to as crossover.

Figure 65 below shows an outline of the evolutionary process taking place in EAs. Compared to more widely known EA-based techniques e.

The main innovative idea in DE is to create offspring from a weighted difference of parent solutions. The DE works as follows: First, all individuals are initialized and evaluated according to the MolDock Score fitness function. Afterwards, the following process will be executed as long as the termination condition is not fulfilled: For each individual in the population, an offspring is created by adding a weighted difference of the parent solutions, which are randomly selected from the population.

Afterwards, the offspring replaces the parent, if and only if it is more fit. Otherwise, the parent survives and is passed on to the next generation iteration of the algorithm. Additionally, guided differential evolution may use a cavity prediction algorithm introduced in Appendix III to constrain predicted conformations poses during the search process.

More specifically, if a candidate solution is positioned outside the cavity, it is translated so that a randomly chosen ligand atom will be located within the region spanned by the cavity.

Naturally, this strategy is only applied if a cavity has been found. If no cavities are reported, the search procedure does not constrain the candidate solutions. Thus, when offspring are created the differences between parental solutions are big, resulting in large step sizes being used. As the algorithm converges to better solutions, the population diversity is lowered, and the step sizes used to create offspring are lowered correspondingly.

Therefore, by using the differences between other individuals in the population, DE automatically adapts the step sizes used to create offspring as the search process converges toward good solutions.

Representation Only ligand properties are represented in the individuals since the protein remains rigid during the docking simulation. Thus, a candidate solution is encoded by an array of real-valued numbers representing ligand position, orientation, and conformation as Cartesian coordinates for the ligand translation, four variables specifying the ligand orientation encoded as a rotation vector and a rotation angle , and one angle for each flexible torsion angle in the ligand if any.

Initialization Each individual in the initial population is assigned a random position within the search space region defined by the user. Initializing the orientation is more complicated: By just choosing uniform random numbers for the orientation axis between To avoid this bias, the algorithm by Shoemake et al. These settings have been found by trial and error, and are generally found to give the best results across a test set of 77 complexes.

The cavity prediction algorithm works as follows: First, a discrete grid with a resolution of 0. At every grid point a sphere of radius 1. It is checked whether this sphere will overlap with any of the spheres determined by the Van der Waals radii of the protein atoms. Grid points where the probe clashes with the protein atom spheres will be referred to as part of the inaccessible volume, all other points are referred to as accessible.

Second, each accessible grid point is checked for whether it is part of a cavity or not using the following procedure: From the current grid point a random direction is chosen, and this direction and the opposite direction is followed until the grid boundaries are hit, checking if an inaccessible grid point is hit on the way. This is repeated a number of times, and if the percentage of lines hitting an inaccessible volume is larger than a given threshold, the point is marked as being part of a cavity.

By default 16 different directions are tested, and a grid point is assumed part of a cavity if 12 or more of these lines hit an inaccessible volume. The threshold can be tuned according to how enclosed the found cavities should be. The final step is to determine the connected regions. Two grid points are connected if they are neighbours. Regions with a volume below The cavities found are then ranked according to their volume.

The clustering is performed on-line during the docking search and when the docking run terminates. Because of the limit of poses, the clustering process is fast.

The members of the pool are replaced by the new cluster representatives found limited by the Max number of poses returned option. The clustering procedure works as follows: 1. The pool of solutions is sorted according to energy scores starting with the best-scoring pose.

The first member of the sorted pool of solutions is added to the first initial cluster and the member is assigned to be the cluster representative. The remainder of the pool members are added to the most similar cluster available using the common RMSD measure if and only if the RMSD between the representative of the most similar cluster and the member is below a user-specified RMSD threshold.

Otherwise, a new cluster is created and the member is assigned to be the cluster representative. When the cluster procedure has terminated, the set of representatives one from each cluster is returned. Supported file extensions: mol2. The remainder is ignored all file formats. If one of the other alternatives should be used, change the order of occurrence in the the file before import.

Notice: Although extensive testing and validation of the import and export of these file formats have been conducted, parsing errors may occur. Found parsing errors can be reported contact Technical Support or send email to [email protected]. Also, purely graphical objects e. Notice that this is only a geometrical check for aromacity.

Otherwise the atom is degraded i. All implicit hydrogens are set to '-1'. If several atom bonds are possible, the atom with highest electro negativity is chosen. If this still results in several possibilities, the atom closest to the current one will be chosen. MD5 Message-Digest Algorithm", under the following license: You may use this software free of any charge, but without any warranty or implied warranty, provided that you follow the terms of the original RSA copyright, listed below.

Created MD5 Message-Digest Algorithm" in all material mentioning or referencing this software or this function. License is also granted to make and use derivative works provided that such works are identified as "derived from the RSA Data Security, Inc.

MD5 Message-Digest Algorithm" in all material mentioning or referencing the derived work. It is provided "as is" without express or implied warranty of any kind. Notice: Some commands require a molecule target: these can be described using the following syntax: Ligand[0] — the ligand with ID 0. Ligand[4,5,6] — the Ligands with IDs 4,5 and 6. Multiple IDs are separated by comma. Ligands — All ligands. By using the plural form of a category, all molecules in it are selected.

Multiple targets can be concatenated using a semi-colon. Notice: The IDs of molecules are based on the order of occurrence in the corresponding Workspace Explorer category. For instance, ligand molecules listed in the Ligands category, begins with index 0 with increments of 1 i. If molecules are removed from the workspace, the IDs of the molecules are changed to follow the new order of occurrence in the list. A lot of operations e. The reference ligand is used to calculate RMSDs while docking.

A File export dialog is opened for selection of a filename. It tries to enforce all hard constraints, and summarizes the soft constraint energy in the console. CAV Invokes Cavity detection dialog.

DUMP [ligand pose ligandenergy poseenergy torsiontree] Shows various debug info about structure. EVAL evaluates the energy of the active ligand. If 'all' is specified hbonds and electrostatic interactions are visualized.

EVAL [all hbond esbonds] If 'hbond' is specified hbonds are visualized. If 'esbonds' is specified electrostatic interactions are visualized. SEED [number] Sets random seed. It shows the current random seed if called without arguments. Loaded modules are also listed. Do not include extension in filename. Adds a molecular surface. If prepended by 'p' the surface will be colored by electrostatic potential. We recommend the carved surfaces for best visualization.

Resolution is typically 0. Don't choose higher resolutions i. The default value of the probesize 1. CLS Clears console log. HIDE [hydrogens labels] Hides either hydrogens or labels. Used for labeling objects. This command is described in detail in the paragraph below.

STYLE [protein pose ligand water cofactor] [vdw, fixed, stick, none] atomScale bondScale Sets the visualization style of specified object.

Rebuilds all objects in the Visualizer Window. Otherwise graphical changes will not be reflected in the GUI. The label command works in the following way: it scans the input-string for known variables like ID, HYB, ELE - see below and replaces them with their value.

Variable Description Atom labels. PC Partial Charge. HYB Hybridization. H, C, N, ELE Element number. IH Number of implicit hydrogens. Shows the total energy of the atom. ETOT This requires that the energy has been evaluated using the 'eval' command. Bond labels. Syntax: 'Label bond string' ID Internal bond index. Type Bond order: single, double, triple, aromatic, Shows the total energy of the bond.

Torsion Tree Labels. Syntax: 'Label tree string'. Torsion Tree labels are evaluated at each rigid component of the ligand. It is only well-defined on poses. EB shows the Bond Energy of the rigid component. Shows the total energy of the rigid component of the tree. Higher values indicate that the rigid component is built later. The rigid root component will have depth 0. Optimal placement of the rigid root will result in a lower maximum depth.

BOND Shows the bond index that this rigid component rotates about. Residue Labels. Some script commands require a molecule target: these can be described using the following syntax: Ligand[0] — the ligand with ID 0.

Ligand[] — the Ligands with IDs from 50 to 60 both included. All — imports all structures. Notice: The IDs of molecules are defined by their order of occurrence in the workspace. All indices are zero-based, meaning that the first ligand will have index 0, the second index 1, and so forth. Notice: Currently, it is not possible to add comments after script commands.

The workspace is not cleared. You can clear the workspace using the NEW command. If only some of them are specified the default parameters will be used for the remainder. Notice that this command will replace the current workspace. No preparation is done on the workspace, since it is assumed that files saved in MVDML format are prepared already.

Notice: LOAD clears the current workspace if any. All molecular structures in the workspace are saved. This can be useful if running several docking simulations of different proteins automated from a scripting language i. Do not use this command when parsing a text-file script as it will terminate the script and not parse anything after the EXIT command. There is normally no need to change these.

The following parameters are available. Determines how torsion terms are evaluated if several torsion angles are available for a bond. Determines if sp2-sp2 bonds should be taken into account. Determines whether ligand self-interaction energy should be taken into account.

Determines whether the protein should be cropped meaning protein atoms outside a given distance is not taken into account.

If crop distance is 0 the default settings the size of the active search space is used. Other the crop distance is defined from the center of the current reference ligand.

If crop distance is negative, all atoms in the protein will be taken into account. Notice that the docking duration increases with the number of atoms. It is advised to keep the default settings of 0. Determines whether ligand torsions are taken into account. Determines whether hydrogen bonding directionality should be taken into account.

Notice: The hbond90 option is not available for the grid evaluator.