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.
- 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.