PC HASL

Installation

HASL programs (Programs Diskette) should be copied to the hard drive working directory ("YOURNAME"), while the contents of the Data/Utilities Diskette should be copied to subdirectories "DATA" and "UTIL" under "YOURNAME." All files generated by HASL will be written to this working directory.

Although the HASL version 3.+ suite of programs was developed to run under DOS 3+, these programs will run under Windows 3+/95 under the DOS option within Windows.

After installation, change your working directory to that containing the HASL programs and files, and type "HASL" to access the Options Menu. The first time HASL is run there are a number of program files created that are subsequently used in the support of various features supported by the program. The Options Menu provides for a degree of user-friendliness during the input of file names, parameter choices, and so on, after which the program launches batch files by shelling to DOS.

Source Code

If you have purchased the HASL Fortran source code, then copy the contents of the HASL source code diskette to your working directory. The file "VHASL.FOR", once compiled, provides the user with a simple way to edit the parameter file and create the command files (or batch files) needed to generate a HASL model. This code was written to function within either a PC(DOS) or VAX (VMS) environment. It should be universal enough to compile and run on other platforms. Of course, VHASL, is written to produce command files suitable only in the VAX(VMS) environment, therefore, the user would need to modify the command file nomenclature and structure accordingly. Creating the HASL executable modules involves compiling and linking the following Fortran source code files:

To compile	VHASL.EXE	use VHASL.FOR
ITERATE.EXE	use ITERATE.FOR
CREATE.EXE	use C1.FOR + C2.FOR + H3.FOR + H4.FOR +i H5.FOR + H7.FOR + H9.FOR + H11.FOR
FIT.EXE	use F1.FOR + F2.FOR + H3.FOR + H4.FOR + H5.FOR + H6.FOR + H7.FOR + H8.FOR + H9.FOR + H11.FOR
MERGE.EXE	use M1.FOR + M2.FOR + H4.FOR + H5.FOR + H9.FOR + H10.FOR
ITERATE.EXE	use ITERATE.FOR
EDITREC.EXE	use EDITREC.FOR

PC-Specific BASIC source code is also included (HASL.BAS and HDRAW.BAS).

The programs and files listed herein are based on those found in the PC version of HASL. For the most part, these are the same files found and generated by the VAX (VMS) version, with some minor exceptions regarding data file nomenclature due to operating system preferences, e.g. RECEPTOR (PC/DOS) and RECEPTOR.DAT (VAX/VMS). The PC version executable codes require that the program DOSXMSF.EXE reside in the same directory (or path) as the HASL executable programs.

HASL .EXE

The main program, HASL (v 3.+) provides a user-friendly interface which facilitates the use of all HASL model-building options. This interface allows the user to set up the parameter file, elect modeling options, create and launch batch files by shelling to DOS, carry out some limited file management, and view (EGA/VGA) 3D renditions of molecules and HASL models.

PARAMS.DAT

This file retains a list of 50 operational parameters which are referred to by other program modules. The parameters include atom type definitions, model resolution amd fitting paradigms.

CREATE.EXE

This module creates a lattice of points describing a molecule based on its Cartesian coordinates and the parameters found in PARAMS.DAT, and saves the resulting set of points in a file called RECEPTOR.

FIT.EXE

This module is designed to use the molecular lattice for each molecule to find the best fit (overlap) of points between a molecule and the RECEPTOR. The fitting routine may involve rotation and translation of the Cartesian coordinates of the molecule (depending upon the options present in PARAMS.DAT). Two files are created after a best fit is found: MOLMOL and RECMOL, containing the Cartesian coordinates of 1st molecule- last molecule and RECEPTOR-last molecule, respectively. These files are accessible to the graphics viewer in HASL.EXE (seeVIEWS).

MERGE.EXE

This module creates a new RECEPTOR file containing lattice points from the original RECEPTOR file and the molecular lattice last-fitted to the RECEPTOR. In this way new molecule/binding data are incorporated into the HASL model. After a set of molecules is merged, i.e., molecule 1 is fitted, then merged; molecule 2 is fitted, then merged, ...etc., then the distribution of partial binding values among the lattice points present in the RECEPTOR is undertaken.

ITERATE.EXE

This module uses the information from the fitting and merging routines described above (located in files HISTORY, RECEPTOR, and ITLIM) to solve the partial binding distribution problem. This is done through an iterative process wherein the sum of partial binding values corresponding to a given molecular lattice of points is compared to the actual binding value for that molecule. A correction is made to the partial binding values throughout the RECEPTOR, and the process repeated for the next molecule, and the next, until the errors in predicted binding values for all molecules in the model are minimized. Once the errors are minimized, the new information is written to the RECEPTOR file, and represents an optimized HASL model.

RECEPTOR (.DAT)

This file contains the working HASL model. It consists of the Cartesian coordinates of the model, the atom type definitions (as set in PARAMS.DAT), the partial binding values at each point and the number of molecules responsible for the inclusion of each point.

ITLIM (.DAT)

This file contains two lines: the number of iterations selected and the error limit.

ITERAT.DAT

This file is generated by ITERATE.EXE and contains a comparison of actual to predicted binding values for the series of molecules being used to construct the HASL model.

HDRAW.EXE

This module is called by HASL.EXE (PC version only) in order to provide an interactive graphical view of several coordinate files: a molecule, HASL (using the RECEPTOR file), previously-fitted molecules, and last molecule-HASL (RECMOL). There is also an option to view the critical binding areas on the last-fitted molecule as derived by the HASL model. All these views utilize an intermediate file generated for viewing purposes (IMAGE.DAT).

IMAGE.DAT

A simple Cartesian coordinate file containing data from either a molecule, HASL model, molecule-molecule (MOLMOL), molecule-RECEPTOR (RECMOL) file in a format read by HDRAW.EXE. The structure of this file is identical to the generic file format found in the molecular HASL Cartesian coordinate file (*.GEN).

HISTORY(.DAT)

This file contains fitting data in the order in which the set of molecules were modeled, along with a listing of HASL points corresponding to the molecular lattice. The information is primarily of use to the ITERATE.EXE module, since it indicates which points in the model correspond to any previously-fitted molecule.

HISTORY.000

This file is used by HASL at the batch file level to null the HISTORY file at certain points in model development. For example, when fitting operations are expected to lead to a new RECEPTOR file, they are preceded at the command level by nulling the HISTORY file so that subsequent use of ITERATE.EXE will reflect only the molecules of interest.

KCAL.DAT

This file contains estimates of binding per atom (as kcal/atom) for the latest-fitted molecule. These estimates are made assuming the binding data is of the form pKi and such log binding data follow the linear free energy relationship, deltaG = -RTlnKi (see Reports, kcal/atom).

MOLECULE.REC & RECEPTOR.REC

Files used by the HASL program for internal reference.

NAMELIST.HSL

This file contains a list of MOL*.FIT names used in the construction of the current HASL model. It is referenced by the program when new data is to be added to a previously saved HASL model.

BATCH FILES

HSERIES.BAT     PC batch file created by HASL.EXE to create a HASL      
                        model from a series of molecules.
TSERIES.BAT     PC batch file created by HASL.EXE to test a series of   
                        molecules on a previously-created HASL.
SERIES.BAT              PC batch file created by HASLEXE to first create a 
                        HASL model from a series of molecules and then test that 
                        model with another series of molecules.


MOL*.FIT &
MOL*.TST                Files containing the molecule file name/activity generated 
by                      HASL.EXE for use by the batch files listed above to access 
                                molecular Cartesian coordinates and binding data.

CARTESIAN COORDINATE FILE TYPES

        *.GEN                   Generic file type (used internally by HASL). 
        *.HSL                   Generic file type containing coordinates of a molecule after 
                                        fitting to the HASL model.
        *.MM2      	        Allinger MM2 file type.
        *.MAC           	Molecular Design Limited file type.
        *.MOL                   Tripos (Alchemy) file type; also seen as *.ALC.
        *.MOL                   Tripos (Sybyl) file type (not directly supported by 
HASL)