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Chemistry Settings

Tautomerization

Tautomerization Settings allow for the customization of various parameters influencing ligand tautomer enumeration and filtering.

Figure 10.10. Tautomerization Settings

General	Effect
Enable popup of tautomer ceneration settings dialog	Enables the settings dialog of the tautomer generation. (default: enabled)
Ignore topological symmetry	If not checked, topologically identical ligand tautomers are discarded even if they are different in 3D structure. (default: enabled)
Max. num. generated tautomers	Specifies the maximum number of unfiltered tautomers to generate. A value of 0 or -1 means no limit. (default: -1)
Max. num. output tautomers	Specifies the maximum number of filtered output tautomers to generate. A value of 0 or -1 means no limit. (default: -1)

Tautomerization Rules	Effect
Tautomerization Rules	Allows you to enable/disable different kinds of common tautomeric rearrangements. If all rules are disabled, no tautomers are generated.

Tautomer Filters

Figure 10.11. Tautomer filters

Tautomer Filters	Effect
Discard tautomers with violated hybridization geometries	If checked, tautomers with atom hybridization states that require a different spatial distribution of the neighbor atoms than the given one are discarded (e.g. sp ² requires a trigonal planar arrangement of the neighbors but the given arrangement is trigonal pyramidal). The setting has only an effect if atom 3D coordinates are available. (default: enabled)
Discard tautomers with sp ³ atoms in planar rings	If checked, tautomeric forms of a molecule with sp ³ atoms in rings that have been perceived as aromatic in the start tautomer are discarded. (default: enabled)
Discard tautomers with non-unique pharmacophores	If checked, each generated tautomer with a molecule pharmacophore that is identical to a pharmacophore of a previous tautomeric form is discarded. (default: disabled)

Force Field: MMFF94

MMFF94 and Minimization Settings allow for the customization of various parameters influencing MMFF94 forcefield energy calculations and the conjugate gradients algorithm used for structure optimization.

Figure 10.12. Force field: MMFF94

Active Scheme

Effect

Active Scheme

Specifies the settings scheme depending on different cases. Binding pocket core molecule energy minimization : If the molecule lies in the active site. Binding pocket side chain energy minimization : the side chains of the binding pocket. Binding pocket core molecule and side chain energy minimization : the core molecule and the side chains of the binding pocket. Free molecule energy minimization : the ligand without environment. Library molecule energy calculation : calculates energies of molecules in a library. (default: free molecule energy minimization)

Energy Contributions	Effect
Energy Contributions	Specifies which types of forcefield interactions are considered and contribute to the overall MMFF94 energy.
Angle bending	If checked, angle bending interactions will contribute to the total energy. Otherwise angle bending is ignored. (default: enabled)
Bond stretching	If checked, bond stretching interactions will contribute to the total energy. Otherwise bond stretching is ignored. (default: enabled)
Out of plane	If checked, out of plane bending interactions will contribute to the total energy. Otherwise out of plane bending is ignored. (default: enabled)
Stretch bending	If checked, stretch bend interactions will contribute to the total energy. Otherwise stretch bend interactions are ignored. (default: enabled)
Electrostatic	If checked, electrostatic interactions will contribute to the total energy. Otherwise Coulomb interactions are ignored. (default: enabled)
Van der Waals	If checked, van der Waals interactions will contribute to the total energy. Otherwise van der Waals interactions are ignored. (default: enabled)
Torsion	If checked, torsion interactions will contribute to the total energy. Otherwise torsion interactions are ignored. (default: enabled)

Parameters	Effect
Distance cutoffs	Allows the specification of distance cutoffs for van der Waals and electrostatic interactions. A value of zero disables the interaction distance cutoff.
Van der Waals	Defines the distance between two atoms up to which a van der Waals interaction is considered to be present. (default: 12.0 Å)
Electrostatic	Defines the distance between two atoms up to which an electrostatic interaction is considered to be present. (default: 0.0 Å)

Electrostatic interactions	Effect
Electrostatic interactions	Definition of the distance exponent and dielectric constant used for electrostatic interaction energy calculations.
Dielectric constant	Specifies the dielectric constant to use for the calculation of Coulomb interaction energy contributions. (default: 1.0)
Distance exponent	Specifies the exponent of the interatomic distance in Coulomb interaction terms. (default: 2.0)

Parameter Set	Effect
Active parameter set	Specifies the parameter set to be used for calculation of MMFF94 energies. (default: MMFF94s enabled)
MMFF94	If selected, the 'dynamic' parameter set will be used.
MMFF94s	If selected, the 'static' parameter set will be used.

Force Field: Minimization

Figure 10.13. Force field: minimization

General	Effect
Optimize atoms on editing	If selected, the edited atoms and bonds (type change, deletion, addition) are optimized automatically. (default: enabled)

Active Scheme

Effect

Active Scheme

Specifies the settings scheme for energy minimization whether a ligand is located in a binding site ( Binding pocket core molecule energy minimization ), a ligand is solely available ( Free molecule energy minimization ), the side chains (including water molecules) of the binding site ( Binding pocket side chain energy minimization ) or the core molecule and the side chains (including water molecules) are minimized. (default: free molecule energy minimization)

Stopping Criteria	Effect
Stopping criterion	Selection of the optimization algorithm stopping criterion. (default: RMS gradient)
Energy delta	If selected, the tolerance value specifies a difference in energy between two optimization iterations. If the calculated energy difference is lower than the specified delta, the optimization is stopped. (default: disabled)
RMS gradient	If selected, the tolerance value specifies the root mean square of the energy gradient components. If the calculated RMS gradient is lower than the specified value, the optimization is stopped. (default: enabled)
Tolerance	Defines the value of the RMS gradient or energy delta (see above). (default: 0.25)
Max. number of iterations	Defines the maximum number of optimization iterations to perform. A value of -1 specifies that the optimization is performed until the rms gradient or energy delta is reached. (default: -1)
UpdateView	If checked, the 3D View will be updated while performing the structure optimization. (default: enabled)

Fixed Atoms	Effect
Fixed Atoms	Definition of SMARTS patterns for the specification of atoms whose position has to be kept fixed during a structure optimization run. In a complex SMARTS pattern (two or more connected atom-patterns matching a substructure) the atoms to keep fixed can be marked by curly braces, e.g. O={C}-O. Otherwise all matched atoms will be fixed.
Fixed ligand atoms	A whitespace separated list of SMARTS patterns describing the ligand atoms to fix.
Fixed environment atoms	A whitespace separated list of SMARTS patterns describing the environment atoms to fix. (default for binding pocket energy minimization: * {[#1]}-[!O,!H2])

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