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Hydrophobicity Software, HINT v2.0, SGI (fwd)
Sender: haney@netcom.com (Dr. David N. Haney)
Subject: WSN: Hydrophobicity Software, HINT v2.0, SGI
Water Structure and Computational Chemistry Scientists:
NEW SOFTWARE PROGRAM - Hydrophobicity
I have seen a number of queries on this forum about hydrophobicity. As
a medicinal chemist and computational chemist, I have frequently asked
some of the same questions about how we could treat what most medicinal
chemists already recognize as a critical property in drug design. Since
hydrophobicity is not an atomistic property, but to some extent a property
of water, we have lacked some valuable tools for drug discovery. I have
learned of work from a group at Virginia Commonwealth University (Don
Abraham, Glen Kellogg) which provides some of these missing tools.
I have found these tools useful in studying a long-term interest of mine,
the interaction of hemoglobin tetramers in sickle cell disease. The
authors have decided to make this software available through a company
called "eduSoft". I provide here a short description of HINT's functionality.
HINT
-New program to evaluate HYDROPHOBICITY at the atomistic level
A new program has recently become available that provides a
functionality long missing from the molecular modeling world.
HINT is a program that performs approximations of atom-based
hydrophobicity based on the hydrophobic fragment work of Hansch
and Leo (C. Hansch and A. Leo, "Substituent Constants for
Correlation Analysis in Chemistry and Biology", Wiley: New York,
1979) and Abraham and Leo (D. J. Abraham and A. J. Leo, Proteins
2:130-152, 1987).
-HINT calculates log P and partitions the information on atoms
HINT is an empirical methodology implemented so that log P can be
calculated for any molecule. The derived atomistic hydrophobicity
information can then be transformed onto a grid or map which allows
graphical contouring to visualize hydrophobic space.
-HINT scores ligand/macromolecule and macromolecule/macromolecule interactions
HINT uses the atomistic hydrophobicity constants as the basis for
an interaction model for the biological environment. Interactions
can be "scored" to model substrate binding or other interactions
such as protein quaternary structure. HINT can also be used in
this way to score orientations from the UCSF DOCK program.
-HINT calculates 3D HYDROPATHY (hydrophobic + hydrophilic) fields
HINT calculates hydropathic (energetics of hydrophobic and
hydrophilic) fields that are useful for 3D visualization of
hydropathy and as a new field with the SYBYL QSAR CoMFA program.
-HINT creates hydropathic complementarity maps
HINT allows the medicinal chemist to construct a hydropathic
map of the inferred receptor based on a series of compounds
with known activity. This hydropathic pharmacophore allows
the medicinal and computational chemist to construct a
pseudo-model of the receptor which provides guidance for
further compound development.
HINT allows the medicinal chemist to construct a hydropathic
map of a know receptor and an inferred complementary map for
potential ligands at the receptor. This latter hydropathic
"complementarity pharmacophore" provides the medicinal chemist
with a model of the receptor which guides further compound
development.
-HINT produces unique 3D hydropathic Interaction maps.
HINT allows medicinal chemists that are designing de novo substrates
and inhibitors to easily visualize the types and quality of the
binding interactions between the ligand and receptor.
HINT allows the macromolecular structure scientist to map and
visualize the interactions within or between proteins or different
protein subunits which pack together. HINT recognizes,
characterizes and displays hydrophobic, hydrogen-bond, and other
non-covalent interactions leading to protein secondary, tertiary,
and quaternary structure.
-HINT is interfaced with InsightII, Sybyl and ChemX
In order to provide easy input and quick visualization of results,
you can use HINT with one of three popular modeling packages.
The InsightII version is fully integrated through Open
Interface. The Sybyl version is implemented through an SPL
program. The ChemX version is implemented through Chemlib. All
versions have the "look and feel" of the host program with
compatible graphical user interfaces.
-Some publications describing uses of HINT
1. G.E. Kellogg, S.F. Semus, and D.J. Abraham, J. Comput. Aided
Mol. Des. 5:545-552,1991.
2. C.S. Wright and J. Jaeger, J. Mol. Biol. 232:620-638, 1993.
3. D.J. Abraham and G.E. Kellogg, 3D QSAR in Drug Design:Theory,
Methods and Applications, pp 506-522, 1993.
4. V.R. Nayak and G.E. Kellogg, Med. Chem. Res. 8:41-49, 1994.
5. T.I. Oprea, C.L. Waller and G.R. Marshall, Persp. Drug Design
and Discovery, in press.
-HINT is available in demo versions for trials
HINT is not public domain software, but a free, full-function
demo version is available for trial with your favorite system.
For further information, please contact me at the address below.
Send information sheets and license requests to:
David N. Haney, Ph.D.
12010 Medoc Ln.
San Diego, CA 92131-1417
Voice:619-566-1127
Fax:619-586-1481
Email:haney@netcom.com
Information Sheet
Name:_________________________________Company:________________________________
Address:_______________________________________________________________________
City,State,ZIP________________________________________________________________
Country:______________________________________________________________________
Phone:______________________
FAX:________________________
Email:______________________
Platform: ____SGI
Tape: ____QIC (DC600A) ____4mm DAT ____8mm Exabyte
hostname (/usr/bsd/hostname):_______________________________
CPU type (use hinv, eg IP12):_______________________________
SGI: sysinfo -s (/etc/sysinfo -s):__________________________
--
************** David N. Haney, Ph.D. ****************
* Haney Associates Phone - 619-566-1127 *
* 12010 Medoc Ln. *
* San Diego, CA 92131 Fax - 619-586-1481 *
************** Email - haney@netcom.com ***************