Nov 28 2022
[ ICM Convert | Optimize | Regularization | Impose Conformation | Edit Structure | MMFF | Torsion Scan | Minimize | Sample Loop | Design Loop | Sample Protein | Sample Peptide | Internal Coordinates Table | Normal Mode | Stack | GAMESS | Waters | Energy Terms ]
To calculate energy, build a molecular surface and for all energy operations you need to convert a PDB file into an ICM object.
To convert a small molecule into an ICM object.
This option optimizes H, His, Asn, Gln, and Pro by maximizing hydrogen bonds and other interactions with the rest of the protein and/or with the ligand.
To perform this optimization
This option is described in detail in the modeling chapter here.
If you have two protein structures with the same atom namse and ALTER records but with different conformations you can impose the conformation of one of the protein structures onto the other.
You can do this by:
Set Bond Type
Set Formal Charge
A tether is a harmonic restraint pulling an atom in the current object to a static point in space. This point is represented by an atom in another object. Typically, it is used to relate the geometry of an ICM molecular object with that of, say, an X-ray structure whose geometry is considered as a target. Tethers can be imposed between atoms of an ICM-object and atoms belonging to another object, which is static and may be a non-ICM-object. You cannot create tethers in ICM-Browser, however, if the project that you have loaded contains tethers between two objects, then they can be displayed:
Set Types This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#set-type-mmff
Set Charges This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#set-chargemmff
Read Libraries This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#read-librarymmff
The torsion scan is based on MMFF94s force field - A few corrections have been added over the years, most notably those from Wahl, Freyss, von Korff & Sander J of Cheminformatics 2019.
To sample the torsion angles.
Cartesian This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#minimize-cartesian
Local This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#minimize
Global This option is described in detail here in the command line manual http://www.molsoft.com/man/icm-commands.html#montecarlo
This option is described in the Loop Modeling section.
This option is described in the Design Loop section.
This option is described earlier in this chapter here.
This option is described earlier in this chapter here.
An easy way to set values of internal coordinates is to edit the Internal Coordinates Table directly in the GUI. Variables are discussed in more detail here: http://www.molsoft.com/man/selection.html#vs_
Normal modes can be used to generate an ensemble of protein structures. For example the method can be used to represent flexibility in the pocket.
To generate an ensemble of structures using normal modes.
About Normal Modes:
Using multiple steps along the normal mode one can generate conformations with multiple amplitude values along each mode, so that larger and smaller movements for each mode are included in the stack. If no "interesting" movements are found in top 10 (slowest) modes, one can try to look at 20. If "interesting" movement happens to be #2 or #3, may be one need only look at top 3 or 5. There is absolutely no reason for the movement of interest to be at a particular rank as the protein may contain other mobile pieces in arbitrary places and numbers. The "interesting" movement may, unfortunately, also just not be there at all because not all movements are described well by the normal mode formalism. If one wants to analyze ‘elementary’ movements individually, it is best to look at pure modes; on the other hand in reality the molecule is moving along multiple modes simultaneously, therefore if a representative set of perturbed conformations is desired, randomly mixed modes may be more representative of the the space of conformational perturbations accessible to a molecule.
Some papers describing Normal Modes in ICM:
Operations which use the ICM Biased Probability Monte Carlo method e.g. docking and loop modeling generate a stack of energy conformations.
MolMechanics/Stack/View will display the conformations of a stack in a table ranked by energy. Each conformation can be viewed by double clicking on the table. A stack file will have the extension .cnf. For example, after running the sample loop algorithm a stack of different loop conformations will be generated.
MolMechanics/Stack/Play This option will play the elements of the stack as a movie. You can set the number of frames for the movie and also select whether you would like ICM to interpolate between each frame. You can save this movie in avi, mpeg format using the Screen-Grabbing Movie options.
MolMechanics/Stack/Add current conformation This option will add the currently displayed conformation to the stack. This is useful for experiments such as multiple receptor docking whereby you dock to a stack of conformations.
MolMechanics/Stack/Store Stack in Object This option takes the current stack and stores it in a compressed form inside the specified object. The compressed stack can then be extracted with the load stack object command. Option stack of the montecarlo command stores the generated stack inside the current object automatically.
To view the stack in gui:
MolMechanics/Stack/Delete Deletes the current stack.
MolMechanics/Stack/Set conf Comparison This option compares the stack as described here: http://www.molsoft.com/man/preference.html#compareMethod and http://www.molsoft.com/man/icm-commands.html#compare
MolMechanics/Stack/Recalculate Energies Recaluclates the energy of a current stack if changes have been made.
This option is described in detail here in the command line manual http://www.molsoft.com/man/E-H.html#gamess
You need to register on the GAMESS website and submit download request:
'Flood' procedure populates a box around the region of interest on the protein with water molecules, generating a stack of low-energy water configurations. 'Quick flood' performs the procedure within the interactive ICM session. For more thorough sampling, it is recommended to use 'Sample Flood' that runs the same procedure in the background.
Try an example:
The energy function calculated for any conformation of an ICM molecular object consists of individual terms described which can be turned on and off using MolMechanics/Energy Terms. These terms are described in more detail here http://www.molsoft.com/man/terms.html
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