View HIFA: Add Column Dialog Box

HIFA: Add Column Dialog Box

Field Values: Interactions
option menu: {All|Hydrophobic|Polar}
Select the mapped interactions to be calculated for the field.

can proceed:

Field Values: Smoothing
option menu: {Box|None}
Setting Smoothing to Box produces smoother HINT maps, but at a cost of approximately an eight-fold increase in calculation time. The algorithm surrounds each actual grid point with a box whose corners are at (+/-)1/3 grid spacing along each cartesian axis. The map is evaluated for each corner of the box and the resulting values averaged to yield the map value at the original grid point.

Receptor Partition Options: Partition Method
radio button set: {Calculate|Dictionary}
HINT offers two methods of partitioning the receptor molecule(s) on this option menu: "Calculate" or "Dictionary". The Calculate method uses the molecule's atom types (Sybyl) and bond connections as input data to the partition algorithm. The Dictionary method relies on a predefined set of predefined data for regularly occurring substructures such as amino acid residues and nucleic acid bases. In this case the input data is the atom names and substructure names/types.

Receptor Partition Options: Hydrogen Treatment
option menu: {United|Essential|All}
This menu describes how the Partitioning will treat hydrogens; there are three options: "United" (using an approach the treats all hydrogens implicitly as part of their parent heavy atom), "Essential" (using an approach that treats (only) polar hydrogens explicitly), and "All". Note that the selection of this parameter has implications in following interaction calculations. For example, hydrogen bonding will be incorrectly modeled by HINT if the United option is chosen. In general the Essential option is best for most applications. The All option appears to "dilute" the hydrophobic density, but treats aromatic hydrogens as potential hydrogen bond donors.

Receptor Partition Options: Solvent Condition
option menu: {Inferred|Neutral|Acid|Base}
This option menu is active only if the "Dictionary" method is chosen. The menu lists four options: "Inferred", "Neutral", "Base", "Acid". The latter three represent the pH conditions under which the molecule is to be partitioned. Inferred represents a special case where each substructure (e.g., residue) will be partitioned based on its hydrogen count. For example, if one aspartic acid in a protein is believed to be protonated while other acidic and basic residues are to remain at neutral pH, using the Inferred Solvent Condition is the appropriate approach. Note that all essential hydrogens must be present in the entire model, not just in the "special" residues.

Receptor Partition Options: Polar Proximity
option menu: {Off|Via_Bond|Through_Space}
This option menu is only active if the "Calculate" method is chosen. When two or more polar groups are in "in proximity" within a molecule, their effects are cumulatively diminished -- this is termed the polar proximity effect and is dealt with by the Leo method of LogP estimation and by HINT as corrective factors to the hydrophobic atom constants. HINT offers three options for Polar Proximity: "Off", "Via_Bond", and "Through_Space". The Via_Bond method is most compatible with the Leo system, and is the option recommended. Through_Space may be appropriate for some larger molecules that have significant intramolecular non-covalent interactions between polar groups. It uses a through-space distance function to estimate the polar proximity effect.

Receptor Partition Options: Through Space Function...
push button
This button, which is only active if Polar Proximity is chosen to be Through_Space, calls the Polar Prox. Dist. dialog to define the specific through-space distance function to be applied to the polar proximity correction.

Receptor Partition Options: Direction Vectors/Parameters...
check box and push button
>Use these options to activate directionality vectors for the molecule partitions. Pressing the Parameters button calls the Direction Vector dialog box.

Set (New) Receptor Data for Ligands...
push button
Two components are necessary for the InterMolecular HIFA Functions: Macromolecules (Receptors) in Sybyl Molecular areas (or .mol2 files), and a Molecular Spreadsheet of ligands both oriented for interaction with these Macromolecules and overlapped in 3D space with respect to each other. This button defines the relationship between the receptors and (row) ligands. In effect, the molecular area (or .mol2 file name) for the receptor corresponding to each ligand is stored in a column of the Molecular Spreadsheet. Pressing this button calls the HINT Receptor MolData dialog to assign the Macromolecule/ligand correspondence.

Assign (Existing) Receptor Column...
push button
Two components are necessary for the InterMolecular HIFA Functions: Macromolecules (Receptors) in Sybyl Molecular areas (or .mol2 files), and a Molecular Spreadsheet of ligands both oriented for interaction with these Macromolecules and overlapped in 3D space with respect to each other. This button defines the relationship between an existing receptor column and the (row) ligands. Pressing this button calls the HINT Receptor MolColumn dialog to assign the Macromolecule/ligand correspondence.

Ligand Partition Options: Partition Method
radio button set: {Calculate|Dictionary}
HINT offers two methods of partitioning the ligand molecule(s) on this option menu: "Calculate" or "Dictionary". The Calculate method uses the molecule's atom types (Sybyl) and bond connections as input data to the partition algorithm. The Dictionary method relies on a predefined set of predefined data for regularly occurring substructures such as amino acid residues and nucleic acid bases. In this case the input data is the atom names and substructure names/types.

Ligand Partition Options: Hydrogen Treatment
option menu: {United|Essential|All}
This menu describes how the Partitioning will treat hydrogens; there are three options: "United" (using an approach the treats all hydrogens implicitly as part of their parent heavy atom), "Essential" (using an approach that treats (only) polar hydrogens explicitly), and "All". Note that the selection of this parameter has implications in following interaction calculations. For example, hydrogen bonding will be incorrectly modeled by HINT if the United option is chosen. In general the Essential option is best for most applications. The All option appears to "dilute" the hydrophobic density, but treats aromatic hydrogens as potential hydrogen bond donors.

Ligand Partition Options: Solvent Condition
option menu: {Inferred|Neutral|Acid|Base}
This option menu is active only if the "Dictionary" method is chosen. The menu lists four options: "Inferred", "Neutral", "Base", "Acid". The latter three represent the pH conditions under which the molecule is to be partitioned. Inferred represents a special case where each substructure (e.g., residue) will be partitioned based on its hydrogen count. For example, if one aspartic acid in a protein is believed to be protonated while other acidic and basic residues are to remain at neutral pH, using the Inferred Solvent Condition is the appropriate approach. Note that all essential hydrogens must be present in the entire model, not just in the "special" residues.

Ligand Partition Options: Polar Proximity
option menu: {Off|Via_Bond|Through_Space}
This option menu is only active if the "Calculate" method is chosen. When two or more polar groups are in "in proximity" within a molecule, their effects are cumulatively diminished -- this is termed the polar proximity effect and is dealt with by the Leo method of LogP estimation and by HINT as corrective factors to the hydrophobic atom constants. HINT offers three options for Polar Proximity: "Off", "Via_Bond", and "Through_Space". The Via_Bond method is most compatible with the Leo system, and is the option recommended. Through_Space may be appropriate for some larger molecules that have significant intramolecular non-covalent interactions between polar groups. It uses a through-space distance function to estimate the polar proximity effect.

Ligand Partition Options: Through Space Function...
push button
This button, which is only active if Polar Proximity is chosen to be Through_Space, calls the Polar Prox. Dist. dialog to define the specific through-space distance function to be applied to the polar proximity correction.

Ligand Partition Options: Direction Vectors/Parameters...
check box and push button
>Use these options to activate directionality vectors for the molecule partitions. Pressing the Parameters button calls the Direction Vector dialog box.

Distance Function...
push button
Select this button to describe the mathematical distance behavior of hydropathy for the current calculation. This button calls the Distance Function dialog box.

Cutoffs: Cutoff Radius
field
The Cutoff radius sets a distance limit for interactions. An interatomic interaction at a range exceeding this value is set to zero.

Cutoffs: Van der Waals Limit
field
The Van der Waals Limit parameter allows limited user control of the HINT Van der Waals radii set. The Van der Waals Limit is a multiplicative factor (default = 1.00) that adjusts the predefined radii set. A value of less than 1 would allow more "bump" between atoms, while a value greater than one would allow less.

Region
radio button set: {Use Pre-existing|Calculate Automatically...|Define...}
Choose the method by which the HIFA region is to be defined. This region must be large enough to encompass the area of interest in all molecules in the spreadsheet. Use Pre-existing means that the region is defined by an existing SYBYL region file on disk. Calculate Automatically... invokes the Calculate CoMFA Region Automatically dialog box which defines the region based on the union space spanned by the molecule set. Define... invokes the Define CoMFA Region dialog box which allows you to enter the region as arbitrary boxes in cartesian space.

HIFA Region File
field and push button
This field specifies the name of the HIFA Region File to be used for creation of the HINT field. If the Region is created by Calculate Automatically... or Define... this field will be filled by a return value from the associated dialog boxes. If the Region is Use Pre-existing, you will have to either enter the name of the region file or select from the supplied list by using the ... button.