Computational Chemistry Community:

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.
	The demo requires that you complete the license attached below
	and return it by email.  Your email address and completed 
	form are accepted as acknowledgement of the terms.  If you
	prefer, a beautified license document can be faxed to you.


HINT PRICING

The general pricing schedule for HINT is shown below.  This includes the 
software with simplified installation, professional manual, and professional 
support for 6 months.  Please do not hesitate to ask questions for more 
detailed information:

                        ACADEMIC        $1000
                        NON-PROFIT      $2000
                        COMMERCIAL      $5000


		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   

Version: _____InsightII, _____Sybyl, _____ChemX

Tape: ____QIC (DC600A)  ____4mm DAT  ____8mm Exabyte

hostname (/usr/bsd/hostname):_______________________________

CPU type (use hinv, eg IP12):_______________________________

SGI: sysinfo -s (/etc/sysinfo -s):__________________________

_________________________________________________________________________________

WARNING: use 132 column window to read below

LICENSE DOCUMENT - cut here
_________________________________________________________________________________________________________

eduSoft, LC
Software Evaluation License Agreement

Between:	eduSoft, LC				And	___________________________________________
		a Virginia Corporation
		PO Box 1811					___________________________________________
		Ashland, VA  23005  USA
								___________________________________________

		"EDUSOFT"						"USER"

USER wishes to license on an evaluation basis the EDUSOFT software described below:

___	Hint 2.0S (for SYBYL)

___	Hint 2.0I (for InsightII) includes Hint 2.0D option for building molecules from SMILES string input.

___	Hint 2.0C (for ChemX)

for a period of __30__ days commencing on the date of execution of the last signator, on a SINGLE CPU (which is 
identified by the information detailed below).

EDUSOFT and USER, for their mutual benefit, hereby agree as follows:

1.	DELIVERABLES.   The term "SOFTWARE" shall mean the computer programs, associated data files, and other 
material including, but not limited to, documentation, manuals, specifications, and training materials related thereto.

EDUSOFT shall deliver SOFTWARE at no charge to USER for the sole purpose of evaluating the capabilities and com-
patibility of the SOFTWARE.  EDUSOFT shall provide support for USER during the evaluation period by assisting in 
installation and by answering usage questions. USER's right to use the SOFTWARE is nontransferrable and nonexclu-
sive and shall be limited solely to USER's evaluation at USER's location and address specified above or as otherwise 
stated in this Agreement.  USER must pay shipping and handling import duties if applicable.

2.	OWNERSHIP AND CONFIDENTIALITY.   EDUSOFT retains title and full ownership rights to SOFTWARE and 
SOFTWARE is asserted to be EDUSOFT's proprietary information comprised of copyright and trade secrets.  USER 
shall make no copies of SOFTWARE other than that necessary to load and run SOFTWARE.  SOFTWARE and any 
other writ-ten material provided by EDUSOFT shall be held in confidence by USER, using at least the same care USER 
provides for USER's own proprietary information.  This information may be disclosed only to employees of USER 
involved in the evaluation.  USER shall appropriately notify each employee to whom any such disclosure is made that 
such disclos-ure is made in confidence and shall be kept in confidence by the employee.  USER shall take whatever 
steps are neces-sary to assure that each employee keeps such confidence.

The obligations of USER shall not apply to any information which it can be demonstrated:
	a.	has become part of the public domain other than by acts or omissions of USER;
	b.	has been made known to USER by third parties as a matter of legal right and without restriction 
on disclosure or use; or
	c.	was in the possession of USER prior to disclosure by EDUSOFT and was not acquired directly or 
indirectly from EDUSOFT.

This obligation of confidentiality shall remain in effect regardless of the termination of this Agreement until SOFTWARE 
becomes part of the public domain.

3.	RESTRICTIONS.   USER shall not (i) permit any third party to use SOFTWARE; (ii) modify or change 
SOFTWARE; or (iii) decompile, disassemble or otherwise reverse engineer SOFTWARE.

USER acknowledges that if problems are encountered with the host software (Sybyl, InsightII, or ChemX) during eval-
uation, USER will notify EDUSOFT of the problems and attempt to isolate HINT-related problems from problems that are 
wholly related to the host software by recreating the problem with the original environment.  The producers and 
distributors of the host software programs (Tripos Associates, Biosym Technologies, and/or Chemical Design) have no 
responsibility for HINT or potential problems caused by the HINT installation, nor do they endorse the HINT software.

SOFTWARE may not be used to create data (e.g., LogP) that is stored in a database for later (i.e., post-evaluation) use.

4.	DISCLAIMERS.   SOFTWARE is provided for evaluation purposes only.  Accordingly, EDUSOFT does not war-
rant that SOFTWARE will meet USER's requirements or that its use will be uninterrupted or error free.  The entire risk as 
to the quality and performance of SOFTWARE is with Licensee (USER).  EDUSOFT SHALL HAVE NO LIABILITY FOR 
DIRECT, SPECIAL, INCIDENTAL, CONSEQUENTIAL, OR EXEMPLARY DAMAGES EVEN IF IT HAS BEEN ADVISED 
OF THE POSSIBILITY OF SUCH DAMAGES.  

5.	COMPLETION OF EVALUATION.   Upon completion of the evaluation, USER shall: (1) acquire from EDUSOFT 
a license to continue using SOFTWARE; or (2) destroy all copies of SOFTWARE and return all documentation and  soft-
ware distribution media supplied by EDUSOFT and notify EDUSOFT in writing that such actions have been completed.

6.	EXPORT.   USER will not export from the United States or reexport from anywhere any part of the SOFTWARE.

USER:							EDUSOFT, L.C.:

_____[email return address]_________________	_____[email return address]_______________________
Authorized Signature for User					Authorized Signature
						David N. Haney, Ph.D.
____________________________________________	_________________________________________________
Printed Name						Printed Name
						Marketing and Sales
____________________________________________	_________________________________________________
Title							Title

____________________________________________	_________________________________________________
Date							Date


The following system information (SGI) is to be Completed by USER to enable license key creation:

hostname		______________________________________________________

CPU type (use hinv): 	______________________________________________________ 

SGI: /etc/sysinfo -s	______________________________________________________

Modeling Host Software:						Tape Media:

SYBYL Release/Version:	________________________		______   QIC

InsightII Release/Version:________________________		______   4mm DAT

ChemX Release/Version:	________________________		______   8mm Exabyte


User Contact:		_________________________________________________________

Phone:			________________________________Fax Number:________________________________

E-mail:			_________________________________________________________

Shipping Address:	_________________________________________________________

			_________________________________________________________

			_________________________________________________________


-- 

        **************  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  ***************