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