INTERCHEM

     INTERCHEM is a general purpose molecular modelling program 
written by two chemists, Drs. Robin Breckenridge and Peter 
Bladon, at the University of Strathclyde.  The original version 
which was mounted on Digital Equipment VAX processors driving 
graphics screens on a range of terminals, has now been  re-
written for use on Silicon Graphics workstations, where the 
superior graphics and computational performance have been 
exploited.

     Throughout the design of the program, attention has been 
devoted to making it easy to use by relatively inexperienced 
people.  In the SGI version of the program, only minimal 
knowledge of UNIX is required.  It is thus possible for beginners 
to obtain useful results without extensive training.

     The aim has been to provide a program which will be of use 
to chemists of all sorts; and to facilitate access to many of 
the well known packages (e.g. MOPAC) which are available for 
computational chemistry.

     The popularity and usefulness of the original version of the 
program at Strathclyde University can be gauged by the over 
10,000 instances of its use over the past 6 years.

     The Silicon Graphics version of the program consists of 
54,000 lines of FORTRAN code. The auxiliary program PROTEINS
used to access the Brookhaven data bank consists of a further
6500 lines.  In addition there are 1.2 Mbytes of data files.
    
     A listing of the main features of INTERCHEM is as follows.

DISPLAY MODES FOR STRUCTURES (simple modes)
     Wire frame display.
     Atom-numbered wire frame display.
     Wire frame display with atom-coded half bonds.
     Wire frame display with coloured chains.
     Red-green stereo wire frame display.

DISPLAY MODES FOR STRUCTURES (with lighting model)
     CPK mode display.
     Atom-coded ball and wire frame  display.
     Cylindrical bonds colour coded for bond-order.
     Cylindrical bonds with atom-coded half-bonds.


SINGLE, DUAL, QUADRUPLE DISPLAY MODES
     Display of a single structure, or of two or four structures 
     simultaneously.  (Structures labelled A, B, C, and D)

MANIPULATION OF STRUCTURES
     Rotation on X, Y, Z, screen axes
     Increase/decrease of size of structure
     Display/hide hydrogen atoms
 
For display modes not involving the lighting effects, 
manipulations occur in real time, even for structures having 
large numbers of bonds and atoms. With structures involving 
lighting models, rotations and scalings occur at acceptable 
rates, but the rate is dependent on the number of atoms.

OPERATIONS ON STRUCTURES
     Centre display on specified atom
     Centre display on centre of molecule
     Move structure on x, y, or z axes of screen
     Calculate bond-lengths
     Calculate non-bonded distances
     Calculate bond angles
     Calculate torsion angles
     Write file of bond lengths, bond angles, and torsion angles
     Write listing file of co-ordinates and connectivities
     Identify chiral centres
     Find molecular formula and molecular mass
     Invert structure about centroid
     Reflect structure in XY, XZ, or YZ plane
     Rotation of chain segment
     Loci of atoms on rotation of chain segment
     View down specified bond
     Remove hydrogens from structure
     Manually renumber the structure
     Re-number structure using Morgan's algorithm
     Find molecular formula, molecular weight, and masses of 
     molecular ions in mass spectrum.

INVESTIGATION OF ENERGETICS OF BOND ROTATION
     Energy profile for rotation of a fragment about one bond
     Energy profile for rotation of a fragment about two bonds
     Energy map for rotation of a fragment about two bonds

STRUCTURE FITTING AND COMPARISON
     Fitting of any of the structures, A, B, C, D on one of the
others by three methods:-
           Three point fit
           Least-squares fit
           Least-squares fit with fragment rotation

STRUCTURE EXCHANGE AND COPYING
     Any one of the structures A, B, C, D may be copied from any 
of the others.
     Any pair of structures chosen from A, B, C, and D may be 
exchanged

STRUCTURE MERGING
     The pairs of structures A and B, or C and D, may be merged 
to give a composite structure.  

     Full control of the process is achieved interactively on the 
screen, allowing the second (mobile) structure to be positioned 
and oriented relative to the first structure.  

     Indication is given to the operator of unacceptable non-
bonded interactions.  

     Merging can be controlled so that a specified distance between 
atoms in the two structures may be met.


STRUCTURE BUILDING
     New structures can be modelled interactively starting from a 
comprehensive library of fragments.
     A previously made structure can be recalled and further modified.
     The current structure can be stored away at any time.

     Building takes place by adding to the current (base) structure a 
chosen fragment. Two basic operations are provided:-
     Form one bond between base structure and fragment
     Form two bonds between base structure and fragment (i.e. 
     make a ring)

Other facilities provided include:-
     Invert base or fragment structure
     Reflect base or fragment structure in XY, XZ, or YZ planes
     Alter atom(s) in base  structure
     Delete atom(s) in base or fragment structure
     Alter bond(s) in base structure
     Delete bond(s) in base structure
     Form bond(s) in base structure
     Remove all hydrogens from base structure
     Add hydrogens to base structure
     Create dummy atoms in base structure
     Copy base structure to fragment area
     Exchange base structure and fragment
     Renumber base structure
     Rotate a mobile side chain in either base structure or 
     fragment

     The option of undoing the last operation is provided, so 
allowing mistakes to be rectified.

     At any stage in the building process, the current base 
structure can be optimised using the molecular mechanics program 
PiFF. This process usually takes only a few seconds. The 
optimised structure is then displayed, and further extension can 
be carried out.

STORAGE OF STRUCTURES
     INTERCHEM has a defined format for storage of structures, 
which is used to store both small and large molecules, including 
the fragments in the fragment catalogue. This format is the same 
as in the original VAX version of the program, meaning that data 
files may be transferred between the two systems.

INTERFACES TO OTHER PROGRAMS
     Structures produced by INTERCHEM can be stored in files with 
formats suitable for submission to other programs:- 

     The molecular orbital programs MOPAC, AMPAC
     The molecular mechanics program PiFF
     The distance geometry program DGEOM 

     The structural data output from these programs may be read back 
into INTERCHEM

     Solvent-accessible surface displays using Connelly's program 
may be produced from INTERCHEM structures, using a version of the 
program bound into INTERCHEM. 

SHAPES AND POTENTIAL OPERATIONS
     A facility is provided to display the accessible surfaces of 
molecules coded to show the potentials at the surface due to 
charges on the atoms.

     The 3-dimensional isopotential surfaces due to the atomic 
charges in molecules may be drawn, and potential contour maps may 
also be produced.

     It is possible to align two molecules, without reference to 
their molecular structures, using as matching parameters, either 
the overall shape of the molecules, or the potentials on surfaces 
surrounding the molecules. (Method of Icosahedral Matching). 

     The potentials surrounding molecules due to the charges on 
the atoms may be displayed projected onto transparent 
encompassing spheres or ellipsoids. 

SPECIAL FACILITIES FOR EXAMINING PROTEIN AND NUCLEIC ACID 
STRUCTURES
     Besides the normal display methods which are available for all of 
these large structures (insofar as they are useful), there are 
special functions available. These include:-

     Colour coded wire frame display to show amino-acid or 
     nucleotide components.
     Display to highlight structural features of proteins and 
     nucleic acids.
     Colour coded wire frame display to differentiate protein 
     chains.
     Display of protein structures as ribbons (also in red-green   
     stereo).

     There are functions to analyse the data contained in protein 
structure files in special ways:-

     Torsion angles analysis.
     Ramachandran and Balasubramanian plots to show protein 
     secondary structure.
     A method to find significant sites in a protein structure.
     
     Protein structures may be truncated selectively, by 
selecting residues, or by retaining all of the structure within a 
defined radius.

     Methods are provided to predict protein secondary structure 
features starting from the amino-acid sequence; four established 
methods are used, and the results from all of these may be 
compared. The predictions may also be edited by the user, and the 
resultant consensus preserved in a torsion angle file.  

     These torsion angle files can be used to build peptide 
sequences into standard INTERCHEM structures automatically. There 
is a choice of preparing backbone only structures, structures 
containing all atoms except hydrogen, or full structures 
containing all hydrogens.  Peptide structures containing 
hydrogens can be made in un-ionised form, in zwitterion form, or 
in forms expected at different pH values.   Provision is made for 
selectively forming S-S linkages, and also for making cyclic 
peptides.  The structures containing hydrogen may be submitted 
for structure optimisation using the program PiFF directly. 
Alternatively, structures may be submitted to the distance 
geometry program DGEOM via special files.

     A comprehensive package for the interactive investigation of 
protein homology is provided. A maximum of 60 sequences 
containing up to 400 amino-acid residues may be compared.  Pairs 
of sequences may be aligned using an implementation of the 
Needleman-Wunsch algorithm.  In addition manual alignment of 
whole blocks of sequences is catered for.  Full 'spread-sheet' 
type operations are also provided; sequences may be moved, 
copied, edited, and stored.  Sequences may be randomised (to test 
for significance of homology), or reversed (to test for sequence 
palindromy).  A method is provided for examining  evolutionary 
relationships between groups of highly homologous sequences.  
This searches for (apparently) simultaneous changes in residues 
in sequences, to find regions in a protein which may be of 
importance to the function of the protein.

     Facilities are provided to translate DNA and RNA sequences 
into protein amino-acid sequences.   Choice of reading frame is 
provided, and in survey mode all three reading frames are tried, 
and a report of the maximal peptide length is given.  The 
complementary nucleic acid strand may be investigated as well.

     If a version of the Brookhaven Protein Data Bank is 
available on the machine (or via a network), then the auxiliary 
program PROTEINS can be used from within INTERCHEM, to translate 
the data into files in standard INTERCHEM format.  PROTEINS may 
also be used from a terminal connected directly to the PERSONAL 
IRIS, or from terminals connected to it via a network.

SPECIAL FEATURES FOR THE EXAMINATION OF CRYSTAL STRUCTURES
     Data files from the Cambridge Crystallographic Data Base may 
be loaded into the system. The symmetry operations of the 
appropriate space group may be applied to give the structure of a 
single unit cell, or alternatively a nest of 27 cells (3 x 3 x 3)
may be formed.  Provision is made for displaying the crystal 
axes, crystal (Miller) planes, and an arbitrary defined axis.
This axis could (for example) an experimentally determined 
principal electric vector etc. A comprehensive editing facility 
is present which allows the cleavage planes of the crystal to be 
exposed. Using this and the merge facility (see above) layering 
of one material on a substrate may be modelled.

MISCELLANEOUS FACILITIES
     Access to UNIX operations
     Display Testcard for Camera setup
  
PROGRAM CONTROL
     With the large number of features and functions provided in 
the program, its control might be thought as likely to present 
some problems.  However, it has been designed to be easy to use.  
Control is achieved by display of very explicit pop-up menus.  
These guide the user to those operations which are permissible at 
each stage. Structure manipulation and some other features are 
controlled by the use of cursor picking on static menus, and in 
some cases the functions of these menus is duplicated by the 
function keys.

COMPUTER REQUIREMENTS

Hardware
     The program is designed to run on a Silicon Graphics 
4D/20G machine (Personal IRIS). There should be at least 8 MBytes 
of memory (but preferably 16MBytes), a 380 MByte disk, and a 125 MByte
tape drive. 
The graphics requirements are 24 bits colour planes (used as 2 x 12 
bits, i.e. double buffering is used), 24 bits Z-buffering, and 8 
bit planes for cursor and over/underlay.  A 19 inch 1280 x 1024 
resolution screen is needed.  These should be regarded as the 
minimum configuration for the hardware, for the program to 
function correctly.  It will run on the later and faster versions 
of the Personal Iris (4D/25 and 4D/35), on models with the 
turbo-graphics option, and on models in the Indigo and Crimson 
series.   It is NOT suitable for the basic Indigo machine however.

Software
     The current version of the program is designed to use 
versions 3.3.x and 4.0.x of the IRIX operating system. In order to 
compile the program on the host machine, the UNIX f77 (FORTRAN) 
and cc (C) compilers must be available.

MANUAL
     INTERCHEM is fully documented in a 250 page manual.  A 
tutorial workbook is planned for the near future.

AVAILABILITY
   The INTERCHEM system comprising INTERCHEM, PROTEINS, and PIFF
is available under license through:- 
Quantum Chemistry Program Exchange, Creative Arts Building 181, 
Indiana University, Bloomington, Indiana, 47405.  
Phone (812) 855-4784.   Fax (812) 855-5539
Email   COUNTSR@IUBACS.BITNET
The license fee for industrial and government users is (US) $2000 
The license fee for academic users is (US) $400 

   Further details of the PROGRAM can be obtained from:- 
Peter Bladon, Department of Pure and Applied Chemistry,        
The University of Strathclyde, Glasgow G1 1Xl, Scotland UK
Phone   041-776-1718   or  +44-41-776-1718  
Fax     041-552-5664   or  +44-41-552-5664
Email   cbas25@uk.ac.strathclyde.vaxa (UK)
        cbas25@vaxa.strathclyde.ac.uk (elsewhere)