MacMolecule version 1.7 © 199092.

All rights reserved. Interactive, 3D Molecular Modeling Curriculum
Development Program, featuring a Video Animation Generation Program, and
a Molecular Image Database.

Eugene Myers and Carlos Blanco

Department of Computer Science

Richard B. Hallick and Jerome Jahnke

Departments of Biochemistry and Molecular and Cellular Biology

University of Arizona

Tucson, Arizona 85721

Conditions of Use of this Program.

The University of Arizona grants you an non-exclusive license to use
this program on the following terms: You may use the program directly or
on a computer network. This program may be freely distributed by any
means, including bulletin boards, provided (1) that there is no fee or
charge for consideration of any kind which is in excess of \$8 (aside
from on-line charges) in distributing the software, (2) The program has
not been altered in any way, (3) All documentation and example files are
included. However, we retain all the rights to this program.

You may NOT: (1) Modify, translate, reverse engineer, decompile, or
disassemble the program or documentation. (2) Remove any proprietary
notices, labels or marks on the program and accompanying documentation.

Any image files that you create with your own data files may be used for
any purpose you choose, including the selling of commercial products. We
request that you acknowledge in your product the use of our work with
the statement \"Image created with MacMolecule © University of
Arizona\". If you wish to use files from the image library released with
MacMolecule for commercial purposes, they are covered by the University
of Arizona copyright, and require prior consent.

The software is provided on an \"as is\" basis, and without warranty of
any kind, including but not limited to any implied warranty of
merchantability or fitness for a particular purpose.

In no event shall the authors or the University of Arizona be liable for
any direct, indirect, incidental, special, or consequential damages
arising from use or distribution of this software. The University of
Arizona also shall not be liable for any claim against any user of this
program by any third party.

Update to MacMolecule 1.5

MacMolecule 1.7 is an updated version of MacMolecule 1.5 which was
previously released in April of 1991. The new features are as follows:
(1) PICS sequences created with the rotate tool can be converted to
QuickTime file format (2) Text explanation of an image file can be added
to the image file, and accessed from a pull-down menu (3) In
ball-and-stick mode, sticks are rendered at diameter \> 1 pixel for
larger molecules.

Purpose

MacMolecule 1.7 is a program designed for creating 3D-images of
molecules for use in teaching molecular structure to students of
biology, chemistry, and allied fields.

Molecules have defined structures, determined by the types and numbers
of atoms in the molecule, the size of the atoms, the orientation of the
atoms in 3-dimensional space, and the covalent and non-covalent bonding
between atoms. The structure of many molecules have been solved by X-
ray crystallography. Databases have been established as repositories of
known structures.

All students of biology and chemistry study molecular structure. In
beginning biology courses, we begin with discussions of the structure of
small biological molecules such as amino acids, lipids, nucleotides,
sterols, sugars, and vitamins. This is followed by analysis of the
structure of larger molecules, particularly proteins, DNA and RNA.
Almost all chemistry and biology textbooks illustrate relevant chapters
with molecular structure diagrams and space-filling models. Biochemistry
texts include images of protein secondary structure features, including
the alpha-helix, beta-sheet, and collagen helix. Protein and enzyme
structure is illustrated with molecules like myoglobin, ferredoxin, or
lysozyme. Molecular biology and genetics lessons begin with a
consideration of the Watson-Crick structure for the DNA double helix.
The problem with a textbook-based approach for students is the
difficulty in learning 3-dimensional concepts. Students are limited to a
single 2D-molecular perspective. Color usage to distinguish different
atoms is often minimal, and relatively few molecules are illustrated due
to publishing costs. The instructor in the classroom often must teach
molecular structure by drawing on the chalkboard or using black and
white overhead transparencies.

With MacMolecule 1.5/1.7, instructors and students can use data from
molecular structure databases, and create color 3D-space models of the
small and large molecules on the computer screen in one of three
user-selectable formats, space-filling, ball-and-stick, and wire frame.
Learning is self-paced and participatory. Users can use pre-existing
image data files or create their own molecular models by writing simple
ASCII files with data on atomic coordinates and identification of
covalent bonds. Users are then able to interactively rotate the image in
the X, Y, and Z coordinates on the computer screen. \"What-if\"
questions are possible, since data files can be user modified with a
text editor. Rotating the molecule on the screen is either via mouse
movement, or automated by defined steps in the X, Y, and Z coordinates
via a dialog box. With automated molecule movement, the images can be
saved to disk as a sequence of PICS images that can be re-played from
MacMolecule 1.7 as an animation sequence, or exported to run in other
programs. The ability to create and play back animations of molecules
rotating in 3-space is currently built into the software. Animated
sequences created in MacMolecule 1.7 can now be converted to QuickTime
files for use in other Macintosh applications that support the QuickTime
file format.

Hardware and System Requirements for MacMolecule 1.7

MacMolecule runs on System 6.05 or later, including System 7. The 32-bit
Quickdraw system document is required in the System Folder. Supported
hardware includes the Macintosh SE/30, II, IIx, IIcx, IIci, or IIfx
(including the 8-24 GC-card), and Quadra. In addition, MacMolecule 1.7
will run on the Macintosh LC and IIsi with an optional math
co-processor. In principle, MacMolecule 1.7 will also run on the
Macintosh LC and IIsi with software emulators of the math co-processor,
but in practice the program execution is too slow to be of practical
value. User feedback on hardware experience is welcome. MacMolecule 1.7
will now support 1-bit screen images. Image quality is very poor for
large molecules, and space-filling models with the 1-bit option. We
strongly recommend the use of 8-bit color whenever possible.

Summary of Commands and Program Options

MacMolecule 1.7 uses the standard Macintosh interface of pull-down menus
with keyboard equivalents, and dialog boxes. It runs under the Finder or
Multifinder. Window size is adjusted by moving the control box in the
lower right corner of the screen.

File Menu: Image files created with a text editor, files provided with
the program, or sequences created with the program as a \'movie\' are
viewed with the \'open\' command. They must be closed with the \'close\'
command before viewing a subsequent image. Exit from MacMolecule 1.7
with the \'quit\' command. Printing of images is also supported through
the \'Page Setup\' and \'Print\' options. \'Save as\' is a new option to
create a new default orientation of an image. Rotate the image to the
desired orientation, and \'save as\' results in a new image file with
the desired default orientation and image type. Note that only data
(re-scaled), and not comments, are saved with this option.

Edit Menu: \'Copy\' of screens to the clipboard for pasting into other
applications is supported. MacMolecule 1.7 is also compatible with
screen capture utilities such as SnapJot ( © Wildflower Software) for
saving cropped images as new files. Note that unless the receiving
application is \'smart\' (such as high-end paint programs), the colors
in the copied image may appear somewhat untrue.

Options Menu: The \'light source\' option allows the user to change the
default angle of illumination of the molecule via a dialog box. The
light source is infinitely far away in the direction given by an x,y,z
vector. The \'molecule view\' option allows a view of the molecule as an
x-y-z rotation from the default X, Y, Z position specified in the image
file.

Rotate Menu: Control of user-interactive molecule rotation tool. When
activated, the molecule is grabbed with the mouse and moved to a new
viewing angle. Computer controlled rotations are also possible. A dialog
box is used to specify the total degrees of rotation (360 is the
default), and the degrees of rotation for each step in the sequence in
the X, Y, and Z directions. Rotation can begin with the default image
location, or a user-selected orientation. An option is offered to save
the sequence of images in a file for later playback. Be aware that such
image sequences can be very large files requiring several megabytes of
free disk space. Also, no image file may exceed 16Mb; this is a
Macintosh- imposed limitation. Sequence playback is much faster than
computer controlled rotations for moderate to large size molecules.
Image generation may be performed \"in the background\" under
MultiFinder.

Playback Menu: Allows \'pause\' of image file sequence. Since Image
sequences will play repetitively, and ad infinitum, you must issue a
\'Close\' command through the \'File\' menu in order to stop image
playback. Alternatively, you can click on the window\'s \'close\' box,
or, if you so desire, you can \'Quit\' the program altogether from the
\'File\' menu. Image playback is also performed \"in the background\"
under MultiFinder.

Text Window Menu: To view or hide an optional text window with text
information about the molecular image. Text information can be added to
the image file as described below. This is a new feature of MacMolecule
1.7, for use in adding didactic information about the molecular
structure.

File Format

MacMolecule 1.7 data files have been modified from MacMolecule 1.0 to
accommodate information about covalent bond locations, the desired
default image form (space-filling, ball-and-stick, wire-frame), and the
atom diameters for ball-and-stick models. MacMolecule 1.5 files can be
read directly by MacMolecule 1.7, or updated by inclusion of text
information for the text pull-down menu. MacMolecule 1.7 will display
MacMolecule 1.0 images, but only in space-filling mode.

MacMolecule 1.7 data files are in ASCII text format. They can be created
and modified with any text editor or word processor that can save files
in text only format. A file for the amino acid glycine is shown as an
example.

; glycine H+

2

;model

BS

C = 1.5, 0.6 (.5,.5,.5)

O = 1.4, 0.58 (1.,0.,0.)

N = 1.5, 0.6 (0.,0.,1.)

H = 0.90, 0.36 (1.0, 1.0, 1.0)

C1 : -3.49503 1.79605 2.15052

C11 : -4.56421 0.74904 1.99995

H1 : -6.12061 1.89748 2.79283

H2 : -6.34809 0.23019 2.87950

H21 : -1.79454 2.28689 1.44555

H3 : -5.30122 0.99524 3.90571

H31 : -4.14040 -0.23229 2.19028

H32 : -4.95760 0.75616 0.99245

N1 : -5.64483 0.98849 2.95291

O1 : -3.56196 2.69996 2.94043

O2 : -2.50337 1.59972 1.31374

;BONDS

C1, C11

C1, O1

C1, O2

C11, H31

C11, H32

C11, N1

H1, N1

H2, N1

H21, O2

H3, N1

glycine

The amino acid glycine is the smallest of the 20 common amino acids
found in proteins. The color scheme used to designate atoms is as
follows: gray = carbon, blue = nitrogen, red = oxygen, white = hydrogen.

Explanation of File Format Line by Line

EXAMPLE 1:

; glycine H+

Example 1 is a Comment Line. Comment lines are optional, and are not
required for image display. Comment lines begin with a semicolon (;),
and are ignored by the program. Comments may also be placed at the end
of data lines. They are ignored by MacMolecule 1.7, and may be placed
anywhere within the file. It is often useful to include comment lines in
image files for large macromolecules. For example, with comment lines
for each residue in an enzyme image file, it is possible to create new
files showing key features of the enzyme structure, such as active site
residues, alpha- helix or beta sheet secondary structure, polypeptide
backbone stripped of side chains, etc. We recommend that users include
in comment lines the relevant literature or data base citations for the
coordinates used to create a new image file. Note that comment lines are
not preserved by the \'save as\' option of the program.

EXAMPLE 2:

2

;model

BS

Example 2 shows the first 2 required data lines, separated by a comment
line. The first data line is a \"2\" to distinguish a MacMolecule 1.7 or
1.5 file from a MacMolecule 1.0 file. The second data line designates
the default molecular model, WF for wire-frame, SF for space-filling,
and BS for ball-and-stick. Both data lines are required.

EXAMPLE 3:

C = 1.5, 0.6 (.5,.5,.5)

Example 3 is a definition line for a type of atom that occurs in the
image. The four atom data lines define the diameters and color for the
atoms used in the image, carbon (C), oxygen (O), nitrogen (N), and
hydrogen (H). Each atom used in the image must be in the file header.
The first two numbers after the equal (=) sign, separated by a comma,
are the user-specified diameters of the atom in Angstroms for the
space-filling, and ball-and-stick models, respectively. We have set the
ball-and-stick radii at 0.4 of the covalent radii in the image library
examples. Other radii may be chosen. The three numbers in parentheses
are the (red, green, and blue) color values chosen to represent the
atoms on the Macintosh color screen, with numbers ranging from 0 to 1.
Note that red is (1 , 0, 0), green is (0, 1, 0), blue is (0, 0, 1) and
white is (1, 1, 1). Custom colors can be created with fractional mixes
of primary colors, e.g., carbon above is gray. Some of the images in the
image library have custom colors for substrates or ligands bound to
enzymes. (Hint: If you know the custom color you want based on the (red,
green, and blue) color values within the \'color\' window of the
Macintosh control panel under the Apple pull-down menu, divide the
values by 65535 to get the corresponding colors in MacMolecule 1.5).

EXAMPLE 4:

C1 : -3.49503 1.79605 2.15052

Example 4 is a data line for atomic coordinates. These data lines are
the 3-space coordinates for each atom in the image file. The first field
is the atom designation, followed by a space, a colon, and one or more
spaces (or a tab). The three numbers are the absolute X, Y, and Z
molecular coordinates in angstroms, separated from one another by one or
more spaces (or a tab). There must be a data line with X, Y, and Z
coordinates for each atom to be displayed. The total number of atoms and
bonds that can be displayed will be dependent on the available memory of
the computer.

EXAMPLE 5:

C1, C11

Example 5 is a data line for a covalent bond. The covalent bonds,
identified as a list following the X, Y, Z atomic coordinates. \"C1,
C11\" specifies a covalent bond in the wire-frame and ball-and-stick
models between the two carbon atoms designated C1 and C11 in the
coordinate list.

EXAMPLE 6:

glycine

The amino acid glycine is the smallest of the 20 common amino acids
found in proteins. The color scheme used to designate atoms is as
follows: gray = carbon, blue = nitrogen, red = oxygen, white = hydrogen.

Example 6 is information to appear in the text window during image
display. The first line is the title for the window. The following lines
appear in the window itself. Text window titles and information are
identified by (option-8, option-8). This information is best placed at
the end of the image file. Text window information is optional, and not
required for image formation.

Creation of QuickTime Files

To create QuickTime files from MacMolecule 1.7 animation sequences, the
SamplePICStoMovie utility provided with the Apple QuickTime Developers
Kit can be used. An example of a QuickTime file created from a
MacMolecule animation is included with MacMolecule 1.7.

Source of Molecular Coordinates

The X, Y, and Z coordinates of atoms in a molecule are normally
determined by means of x-ray crystallographic analysis. The structures
of several hundred macromolecules, and thousands of small molecules have
been solved using this technique. Coordinates are obtained from the
primary scientific literature, or from one of two structural Databases.
The Cambridge Structural Database (CSD), University Chemical Laboratory,
Lensfield Road, Cambridge CB2 1EW, United Kingdom is the source for
small molecule coordinates, and the Brookhaven Protein Data Bank,
Chemistry Department, Brookhaven National Laboratory, Upton, New York,
USA is the source of large molecule coordinates.

Image Library

An Image Library, which was previously released with MacMolecule 1.5,
was designed to give representative examples of space-filling models of
small molecules, proteins, and nucleic acids. A few new images are added
to the MacMolecule 1.7 release, including the complete structure of a
transfer RNA molecule and a zinc finger protein-DNA complex. We have
used the following color scheme for the image library: Red is oxygen,
gray is carbon, blue is nitrogen, white is hydrogen, and yellow is
sulfur. Other atoms are given special colors.

Correspondence with the Authors

Please address correspondence about MacMolecule 1.7 (c) 1990-1992 to Dr.
Richard B. Hallick, Department of Biochemistry, Bioscience West 524,
University of Arizona, Tucson, Arizona, 85721, U.S.A. FAX: 602-621-9288.
Email address: Internet, hallick@arizona.edu.

Technical questions can also be addressed to Mr. Jerome Jahnke. Email
address (internet): jahnke@joplin.biosci.arizona.edu, or Compuserve
76066,612.

We would appreciate learning about your experiences using MacMolecule,
and receiving copies of user-created image files that can be
incorporated into the image library distributed with the software.
Future updates to MacMolecule will be released by anonymous FTP at
joplin.biosci.arizona.edu. User contributed image files will also be
made available at this address, and bundled with future releases.

Please notify us if you have found any incompatibilities between
MacMolecule 1.7 and any other software product or if you think that you
have discovered a \"bug\" in the program. We would appreciate as
detailed a description of the error as possible. Also, send E-mail to
one of the above addresses for any technical questions that you might
have regarding the program\'s limitations, user interface, and
functionality.

Acknowledgments

The crystal lattice images were created by Peter Hardman, Surface
Science Centre, Manchester University, Oxford Road, M13 9PL.
(Hardman@uk.ac.mcc.cgu.v2). He has written a program called \"Lattice
Maker\" to automate file creation. Lattice Maker is available by
anonymous FTP at sumex-aim.stanford.edu.

Revison History

v1.7

1\) Fixed PICS generator for creation of QuickTime Movies

2\) Added floating Text window for description which can be included in
image files.

3\) Fixed bond resolving so it looks better when atoms are smaller.

4\) Resolution of images is a bit better and faster (not that you would
notice).

v1.5.1

1)Fixed remote bug which occured on any machine with internal video
running system 6.0.x and UniFinder.

v1.5

1\) Supports Ball and Stick, Wire Frame, and Space Filling models.

2\) Background color is user selectable.

3\) Hardware requirements were modified. MM will now support 1 to 32 bit
video (it will only resolve as 8 bit).

4\) Memory Management has been changed there is no upper limit on atom
numbers.

5\) MacMolecues window can be resized.

6\) System 6.0.5 is required, as is 32 bit QuickDraw.

v1.0

1\) First release of MacMolecule.

Image Revison History

> Images Included with MacMolecule 1.7
>
> (Compatible with Ball-and Stick, Wire-Frame, and Space Filling
> Imaging)
>
> A Few New Images:
>
> 5\'-yGMP in yeast phenylalanyl tRNA Phe, biotin, glycine (sample file
> from \'About MacMolecule\', yeast phenylalanyl tRNA Phe complete, Zinc
> finger-DNA complex, triple nucleotide base pairing from a tRNA,
> apolipoprotein 3B alpha carbon trace, triose-phosphate isomerase
> backbone and beta carbons
>
> VSPER Models (Valence Shell Electron Pair Repulsion. Image Files
> provided courtesy of Dr. C. Eugene Burchill, Univ. of Manitoba):
>
> Electron pair conformations: linear, trigonal planar, tetrahedral,
> trigonal bipyramid, octahedral
>
> Inorganics (Image Files provided courtesy of Dr. C. Eugene Burchill,
> Univ. of Manitoba):
>
> amide ion, ammonium ion, beryllium chloride, boron trichloride,
> bromine pentafluoride, carbon dioxide, chlorate ion, HCN, hydroniu
> ion, iodine trichloride, nitrate, nitrite, phosgene, phosphorus
> pentachloride, phosphorus trichloride, silicon tetrachloride, stannous
> chloride, sulfate ion, sulfur dichloride, sulfur dioxide, sulfur
> hexafluoride, sulfur tetrafluoride, triiodide ion, water, xenon
> difluoride, xenon tetrafluoride

Images Included with MacMolecule 1.5/1.5.1

(Compatible with Ball and Stick, Wire-Frame, and Space Filling Imaging)

> Amino Acids:
>
> D-alanine, D-tryptophan, D-tryptophan(H+), di L-leucine(H+),
> glycine(H+), L-alanine, L-arginine(H+), L-asparagine, L-aspartate(H+),
> L-cysteine(H+), L-glutamate(H+), L-glutamine(H+), L-histidine(H+),
> L-isoleucine(H+), L-leucine(H+), L-lysine(H+), L-methionine(H+),
> L-phenylalanine, L-proline(H+), L-serine(H+), L-threonine,
> L-tryptophan, L-tyrosine(H+), L-valine(H+)
>
> Peptides:
>
> 2(L-ala-L-ala-L-ala), L-ala-L-ala-L-ala (in beta sheet conformation),
> 3 anti-parallel beta sheets, alpha-L-glu-L-glu, gly-tyr,
> L-ala-gly-gly, L-alanyl glycine, L-alanyl-L-serine, L-cys-L-cys-cyclic
> disulfide, L-seryl-glycine, L-trp-L-met-L-asp-L-phe-, L-tyr-L-phe
> (H+), L-tyr-L-tyr-L-tyr
>
> Nucleotides:
>
> deoxycytidine 3\'-monophosphate, deoxyguanosine 3\'-monophosphate,
> adenosine 5\'-monophosphate, cb3717 (anti-cancer, tetrahydrofolate
> analog), cytosine 5\'-monophosphate, deoxyguanosine-deoxycytidine base
> pair, deoxyguanosine 5\'-monophosphate-deoxycytidine 5\'-monophosphate
> base pair, guanosine 5\'-monophosphate, GMP-GMP dinucleotide, nicotine
> adenine dinucleotide (reduced), S-adenosyl homocysteine, uridine
> 5\'-monophosphate, uridyl-3\'-vanadate (RNAse A inhibitor)
>
> Other Biologicals:
>
> heme group from myoglobin, penicillin G, vitamin A, vitamin B12,
> chlorophyllide B with hydrogens, chlorophyllide B without hydrogens,
> alpha-D-glucopyranose, chlorophyllide A
>
> Small Molecules:
>
> oxygen, phosphate anion, picrate anion, water, cyclohexane in chair
> conformation, diethyl ether, formate anion, methanol,
> buckminsterfullerene, carbon dioxide, cyclohexane in boat
> conformation, benzyloxy proline (H+)
>
> Ribonuclease Images:
>
> Entire enzyme with active site residues and bound inhibitor, active
> site cluster, residues 80-86 (beta sheet), residues 98-103 (beta
> sheet), residues 43-48 (beta sheet), residues 79-87 (beta sheet),
> residues 80-85 (beta sheet), residues 3-13 (alpha helix), residues
> 4-12(alpha helix)
>
> DNA/RNA:
>
> d(GGCC)-d(GGCC) 4 base pairs, DNA double helix of 12 base pairs, GCGG
> RNA tetranucleotide, yeast phenylalanyl tRNA AA stem and CCA, yeast
> phenylalanyl tRNA complete (not included in early releases of this
> image library)
>
> Protein Chains:
>
> myoglobin backbone without heme ligand, thymidylate synthase complexed
> with antifolate analog and substrate, myoglobin backbone with heme
> ligand, alpha carbon backbone of FAB L1 fagment, alpha carbon trace of
> myoglobin
>
> Crystal Lattices: (Courtesy of Dr. Peter Hardman)
>
> Bisco Model 2, Stepped TiO2 (100)
>
> Images Included with MacMolecule 1.0
>
> (Space Filling Imaging Only; Compatible with Later Versions of
> Program)
>
> Amino Acids:
>
> All 20 common amino acids, with and without hydrogens.
>
> Nucleotides:
>
> 3\',5\'-Y-GMPP of yeast tRNA Phe, 5\'-CMP (2\'-O-methyl), 5\'-CMP,
> 5\'-CMP (5-methyl), 5\'-GMP, 5\'-pseudoUMP, ADP, ATP, dUMP
>
> Organics:
>
> cesium crown ether, cyclohexane boat, cyclohexane chair, helicene
>
> Small Biologicals:
>
> carbon dioxide, chlorophyllide B, cholesterol, dUMP, folate analog,
> glucose, heme ligand of myoglobin, NAD, oxygen, penicillin G,
> phosphate anion
>
> Peptides/Proteins:
>
> alpha helix and turn backbone only, H-helix of myoglobin, example of
> beta sheet with 13 amino acids (with and without side chains),
> ferrodoxin, chick lysozyme, myoglobin helices with heme ligand,
> oligosaccharide of NAM-NAG-NAM (lysozyme inhibitor), pig insulin (with
> and without side chains), RNAse A helical segments 1-14 and 3-12,
> RNAse A beta sheets, thymidylate synthase beta sheets
>
> DNA/RNA:
>
> (dCGCATATATGCG)2, (dCGCATATATGCG)2 with backbone, AU base pair in
> yeast tRNA Phe, CG base pair in yeast tRNA Phe, dGC base pair in DNA,
> dTA base pair in DNA, dTG-dAC base pairs stacked, yeast tRNA Phe
> nucleotides 27-43, yeast tRNA Phe backbone