Found as Hint under "eslc". The HINT command allows you to calculate
LogP for small organic molecules, compute 3D maps of hydropathy and
hydropathic interactions, and analyze and quantitate atom-atom
interactions in the biological environment. Selection of Hint
reveals four submenus: Partition, HintMap, HintTable, and HintQSAR.
The first three represent the typical steps of a HINT calculation
while the HintQSAR submenu contains some utilities for use with the
SYBYL Molecular Spreadsheet.
The Partition submenu contains commands which setup and perform the
LogP atom partitition functions. A molecule's partition
is the LogP for octanol/water solubility. This number which has
significance on its own for Medicinal Chemistry and drug design is
reported by the Partition commands. A typical HINT calculation begins
by partitioning one or more molecules to assign HINT interaction
parameters to the atoms of the molecules.
The one option in this submenu is Molecule...
The Partition Molecule Dialog Box defines the setup of the
partition calculation for a molecule that is currently
displayed in SYBYL. There are two Methods of LogP
determination used by HINT: "Calculate" using the SYBYL atom
types and connection matrices, or "Dictionary" using atom
names and predefined HINT parameters for registered
substructure types such as amino acid residues. This dialog
also assists in the setup of several other parameters for
molecule partitioning.
View Partition Molecule Dialog Box
The Polar Prox. Dist. Dialog Box assists in defining a
distance function for use with the Through_Space Polar
Proximity option for Partitioning. Two Functional Forms
with tailorable parameters are available in the Dialog.
View Polar Prox. Dist. Dialog Box
The HintMap submenu contains the commands to execute the HINT
map creation for Molecules, InterMolecular and IntraMolecular
interactions, for Complementary species, and to calculate
difference maps from two input maps. It also contains the
Contour command for contouring HINT (or other) 3D maps.
The six options on this submenu are: Molecule...,
InterMolecular..., IntraMolecular..., Complement...,
Difference..., and Contour...
The Map Molecule dialog box defines the parameters and
molecule necessary for creation of a HINT Hydropathic
field grid that maps the 3D hydropathy of the molecule.
View Map Molecule Dialog Box
The Map IntraMolecular Dialog Box sets up and executes a
HINT calculation on a single molecule to map the
non-covalent interactions within the molecule (e.g.,
folding).
View Map IntraMolecular Dialog Box
The Map InterMolecular Dialog Box sets up and executes a map
calculation of the non- covalent interactions between two
molecules or subunits. Typical uses would be to map the
interactions between a ligand and a receptor, or between two
protein subunits.
View Map InterMolecular Dialog Box
The Map Complement Dialog Box defines parameters and
the molecule for calculating a projected hydropathic
map of a unknown "complementary" species based on the
structure and hydropathic species of a known species.
Another terminology would be to refer to the complementary
map as a "key" map if the known species is a receptor.
View Map Complement Dialog Box
The Map Difference Dialog Box enables you to calculate the
difference (or sum) of two separate HINT (or other) contour
files. The Difference between two HINT Molecule maps for
two related molecules can be used to determine the areas
where hydrophobicity is enhanced, etc. The Difference
between two HINT Interaction maps reveal the effects on
InterMolecular or IntraMolecular stability of site-directed
mutagenesis or other chemical changes on the involved
molecule(s). Note that the validity and interpretability
of a map difference result is enhanced when the two input
maps match closely in terms of region spanned and grid
spacing.
View Map Difference Dialog Box
The Map Contour Dialog Box is a convenience utility for
contouring and displaying SYBYL (.cnt) contour files.
View Map Contour Dialog Box
The Region Definition Dialog Box assists in describing
the region in 3D cartesian space that the map calculation
should span.
View Region Definition Dialog Box
Parameters in the Distance Function Dialog Box control
the functional form of the HINT calculation with respect
to distance between atoms (for HintTable calculations)
or between atoms and grid points (for Map calculations).
View Distance Function Dialog Box
The HintTable submenu contains the commands to execute the
HINT interaction table creation for the InterMolecular
and IntraMolecular cases.
The three options on this submenu are: InterMolecular...,
IntraMolecular..., and Optimize Ligand....
The Table IntraMolecular Dialog Box sets up and executes a
HINT calculation on a single molecule to tabulate and
categorize the non-covalent interactions within the
molecule (e.g., folding).
View Table IntraMolecular Dialog Box
The Table InterMolecular Dialog Box sets up and executes
a HINT calculation between two molecules that are
interacting in some way with one another. This
calculation tabulates and categorizes the non-covalent
interactions involved in ligand or substrate binding or
protein-protein interactions.
View Table InterMolecular Dialog Box
The Small Ligand Optimization Dialog Box sets up
and runs a calculation that uses the HINT "force field"
to optimize the position and orientation of a
small ligand such as water in the model.
View Small Ligand Optimization Dialog Box
The HintQSAR submenu contains some utility functions to
aid in the use of HINT with the SYBYL QSAR module.
Most of the HintQSAR functionality is associated with
the SYBYL Molecular Spreadsheet. This will be discussed
in the next section.
The three options available in the HintQSAR submenu are
Add Hint Score Columns to MSS, Graph HintQSAR... and
Fill MSS Cells with HintCoMFA Field.
This option will add the seven HINT Score categories
(from InterMolecular HintTable calculations) as columns
in an open Molecular Spreadsheet. These seven
descriptors of interaction (Hydrogen Bond, Acid-Base,
Hydrophobic-Hydrophobic, Acid-Acid, Base-Base,
Hydrophobic-Polar and Total) provide a rather complete
description of the interactions between two species,
typically receptor and ligand. Entering these in the
Molecular Spreadsheet, referenced by ligand (Molecule2
by definition), will allow multivariate analysis of the
HINT binding data against physical or biological
properties of the ligand. The Add Score to Current
Spreadsheet option on the Table InterMolecular Dialog
Box will place the HINT Score data in the correct
column/row of the Spreadsheet at the conclusion of the
HINT calculation.
The Retrieve HintQSAR Dialog Box is a convenience
function to facilitate creation (for graphing) of the
CoMFA coefficients*standard deviation contour maps for
PLS runs where the HINT hydropathic field was included.
The dialog box enables selection of the desired field
information and writes the selected CoMFA fields to
scratch disk files. Then these fields are sequentially
contoured.
View Retrieve HintQSAR Dialog Box
This command allows you to fill specified MSS cells with the
HintCoMFA field. You may wish to use this option if you
are attempting to predict activity of a new compound with
a CoMFA model that includes the HINT field.
View Fill MSS Cells with HintCoMFA Field Dialog Box
HINT provides added functionality to the molecular
spreadsheet. Four additional column types are defined
by HINT: HINTLOGP, HINTSCORE, HINTCOMFA and HIFA. These are available
through the Spreadsheet "Autofill" button in the list
of column types. Note: Occasionally the HINTCOMFA and HIFA
column types are dropped by the Autofill menu. If this
happens, type mss!reset_eslc to the Sybyl> prompt.
The Add Column (HintLogP) Dialog Box sets the
parameters for filling the cells in a spreadsheet
column with the partition coefficients of each
molecule (row) in the table.
View Add Column (HintLogP) Dialog Box
The HINTSCORE: Add Columns Dialog Box sets the
parameters for filling the cells in spreadsheet columns with the
Table scores for A) docking each ligand (row) of the Spreadsheet
with a common (rigid) receptor model; or B) calculating an
IntraMolecular Table/Score for each conformer (row) of a molecule
in the spreadsheet.
View HINTSCORE: Add Columns Dialog Box
The Add Column (HintCoMFA) Dialog Box sets the
parameters for filling each cell in a spreadsheet
with the HINT hydropathic field. This Dialog Box
contains parameters related to the initial
Partitioning of each molecule and parameters related
to the HINT map creation for each molecule (row) in
the table.
View Add Column (HintCoMFA) Dialog Box
The HIFA: MSS Dialog Box sets the
parameters for filling each cell of the column with HINT interaction
maps (fields). This is an extension of CoMFA where the field for each
ligand (row) is not the properties of molecule row, but instaed the
interactions between that ligand and its macromolecular receptor.
This Dialog Box contains parameters related to the partitioning
and interaction properties of both the ligand and macromolecule.
View HIFA: MSS Dialog Box
This dialog box is called from the HINT CoMFA or HIFA routine
and is used to set the parameters for defining the
CoMFA region based on the union space spanned by the
entire molecule set. The routine determines the
spatial extents of each molecule and creates a region
that encompasses all molecules.
View Calculate CoMFA Region Automatically Dialog Box
The Define CoMFA Region Dialog Box is used if the
cartesian coordinate set defining the region (Lower
Box Corner, Upper Box Corner) is known, or if a
custom region that includes more than one Box is
needed. This latter case may be a useful option for
some CoMFA experiments where much of the molecular
structures are identical and a "closeup" on the
areas of difference is appropriate.
View Define CoMFA Region Dialog Box
This dialog box is called from the HIFA routine
and is used to set the parameters for defining the
biomacromolecular model(s) coinciding with the ligands
in the spreadsheet rows.
View Receptor MolData Dialog Box
This dialog box is called from the HIFA routine
and is used to define the column containing
biomacromolecular model(s) associated with the ligands
in the spreadsheet rows.
View Receptor MolData Dialog Box