View HINTCOMFA: Add Column (HintCoMFA) Dialog Box

HINTCOMFA: Add Column (HintCoMFA) Dialog Box

Field Values: Map Type: option menu: {Molecule|Complement}; This option allows you to choose whether to make a Molecule-type hydropathic field map or a Complement-type hydropathic field map which extrapolates further into unoccupied regions of space. For most usual applications you should choose the Molecule Map Type.
Field Values: Information: option menu: {Hydrophobic/Polar|Hydrophobic only|Acid/Base}; Set the Information parameter to the type of map information you wish. The three options are: Hydrophobic/Polar (negative field values represent polar regions of space, positive field values represent hydrophobic regions of space); Hydrophobic Only (all negative field values are set to zero); and Acid/Base (negative field values represent basic regions of space, positive field values represent acidic regions of space, hydrophobic regions are set to zero)
Field Values: Acid Base Definition: option menu: {Coulombic|Bronsted|Lewis}; The Acid Base Definition parameter specifies what model for acids and bases will be used by HINT if Information is set to Acid/Base. These definitions are static; they are based on the SYBYL atom types and are not dynamically reevaluated. Three models are available as options:; Coulombic is a formal charge-based model. Atoms with formal positive charges are considered to be acids and atoms with formal negative charges are considered to be bases.; Bronsted uses the Bronsted-Lowry theory of acids and bases. An acid is a proton donor while a base is a proton acceptor.; Lewis uses the Lewis theory of acids and bases. An acid is an electron pair acceptor and a base is an electron pair donor.
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.
Field Values: Include SASA in Calculation: check box; Normally HINTCoMFA applies the Solvent Accessible Surface Area (SASA) of each atom to create the field map (see Theory). This option allows this to be disabled, thus creating a HINT field that has only the raw hydrophobic atom constants.
Field Values: Use Internal Grid Resolution Scaling: check box; HINT has an internal scaling function that multiplies each grid point by the volume of it's grid cube. This serves to normalize the total field for different grid resolutions. The idea is that the total field exerted by a molecule is independent of the resolution it is measured at. This check box option allows you to turn this feature off, that is no internal resolution scaling will be done.
Partition Options: Partition Method: option menu: {Calculate|Dictionary}; HINT offers two methods of partitioning the molecule 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.
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.
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.
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.
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.
Partition Options: Direction Vectors/Parameters...: check box and push button; Use these options to activate directionality vectors for the molecule partition. 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: Inside Mol Cut Off: check box; The Inside Mol Cut Off parameter specifies whether grid points inside the Van der Waals radius of any atom are to be set to predefined constant values.
Cutoffs: Polar: field; The Polar Cutoff parameter is the constant that will be assigned to negative-valued grid points inside the Van der Waals radius of any atom if Inside Mol Cut Off is set to On.
Cutoffs: Hydrophobic: field; The Hydrophobic Cutoff parameter is the constant that will be assigned to positive-valued grid points inside the Van der Waals radius of any atom if Inside Mol Cut Off is set to On.
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 CoMFA 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.
CoMFA Region File: field and push button; This field specifies the name of the CoMFA 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.