Instructions for Use of the MacroModel Program.

1. The left mouse button is used to select menu items, and also to "focus" a window, ie establish communication between it and the keyboard from which file names etc can be typed.
2. The middle button is used to rotate the molecule in the drawing window. The sense of rotation is selected from the main button windows by clicking on ROT X (or Y or Z). By default, both ROT X and ROT Y are selected, and moving the mouse whilst holding down the middle button will rotate the molecule about these two axes. To reset the default, "double click" on ROT X.
3. The right hand button is used to bring help. For example, clicking with this button on a menu item opens up the Help window, with suitable comments.

• To start a carbon chain, click DRAW in INPUT and click on the molecule window with the left mouse button to start a chain. You can rotate the structure whilst building by pressing the middle mouse button and "dragging" the mouse around. In this way, you can impart a realistic 3D component to the molecule you are building. Alternatively, pressing the right mouse button enables you to "translate" the molecule without rotating it.
• There are some organic "templates" defined on the INPUT menu. If these are more appropriate, select one of these instead of DRAW and position it in the middle of the screen. Other templates can be introduced by selecting PEPTID, NUCLEI or CARBO from the menu.
• To continue building up a chain, move the cursor and press the left button again. A line will appear on the screen, representing a C-C bond. If you have a template to which you want to attach a chain, select DRAW, and position the cursor at the atom you want the chain added to. This may create a pentavalent carbon, and you will have to use H DEL (see below) to delete eg a hydrogen and H ADD to add them. If you click once on these two menu items, the action performed will be on a single atom only, but if you double-click, a new menu pops up with several options;
  
  
  
  Quite a number of menu items are of this kind, but you only find out which by trying.
• Continue building up the chain. If you want to close to a cyclic compound, position the cursor accurately on the first atom. If you want a double bond, back-track to the previously positioned atom in the chain.
• One frequently needs to break the chain, ie to lift the imaginary pen you are drawing with off the paper, ie when returning to a previously defined single bond to turn it into a double or triple bond. To do this, simply select DRAW again. To enter carbon side-chains, first select DRAW, then point to the carbon carrying the side chain and then start building up a new chain. After this chain is complete, the "pen" must be lifted off the paper as described above. Complete all the basic skeleton of the molecule in this manner, representing all heteroatoms by carbon at this stage.
• To substitute any carbon atom by a heteroatom, left click on the heteroatom in the INPUT menu, then point to the carbon to be substituted. If you want to insert say four oxygen atoms, point to O on the menu, then to each of the four carbon atoms in turn.
• To delete a specified atom, click on DELET once, then point to the atom to be deleted, or to the middle of a bond if you want to change a double into a single bond. To remove a single bond, you have to first turn it into a "zero order" bond (used for weak complexes, transition states etc) and then delete the zero order bond. This is another "double-clickable" item;
  
  
  
  
• If the structure you are drawing is too big for the screen, it can be rescaled by selecting the SCALE option. Clicking SCALE twice rescales to exactly the size of the screen. Alternatively, if you want to magnify part of structure, select CLIP and point the cross-hair at the bottom left and top right of the region of the molecule to be magnified.
• Carbon chains so drawn have no hydrogens, whereas templates do. Very probably at this stage, the carbon valencies are not correct, most missing hydrogen and the templates may have too many. To ensure correct valency, double click on H DEL and then on H ADD to ensure the correct valencies. If these are wrong, the program will not minimise the structure correctly.
• When the basic elements of the structure are complete, select the ENRGY menu. Several default options are selected automatically, including the MM2 force field. Click on another force field if you want tho change this option. Select START to commence geometry optimisation. You will be asked to enter a job file name. Select New and type the name of a file, e.g. temp. Notice that the keyboard is only active for this purpose if the cursor is positioned over the rectangular box in which the file name is entered and a type cursor appears.
  
  From now on, information about the state of the optimisation appears in the message window. If that window is obscured (e.g. by the Options window) you may have to move it by pressing the left mouse button on the top bar of the window and "dragging" the menu to a new location..The geometry on the screen will be updated as the optimisation proceeds, giving some idea of how the shape of the molecule is changing. If your 3D sketching has not given the program a good enough indication of the three-dimensional structure of the molecule, the optimisation may not converge to a sensible answer. Alternatively, your starting point may converge to the wrong conformation (such as boat rather than chair in a cyclohexane ring).You have to select the INPUT option to make appropriate alterations, and minimise again. Several cycles of this may be needed before a satisfactory result is obtained. You should particularly check that you have the correct stereochemistry. For example, if you think you are working with a cis-alkene, make sure the program has not rearranged it to a trans-alkene when you were not looking! There are also some 'local minima' in the MM2 or MM3 potential energy surface which have very high energies. If an energy makes no 'chemical sense', you should look very carefully at the geometry.
• When optimisation is complete, you are now ready to calculate parameters such NMR coupling constants.
  
  Enter the ANLYZ menu in MacroModel, then select NMR, and finally COUPL. With the left mouse button, click at two hydrogen atoms whose nmr coupling constant you want to predict. The MacroModel program calculates the dihedral angles between these hydrogens, applies the appropriate Karplus relationship (for which a reference is given) and displays the expected value.
  Note: Record all the values in your laboratory notebook, since there is no easy way of printing.
• Save your work using WRITE. Place the mouse cursor in the first rectangular entry window (just below the Write caption) so that a type cursor appears and type a name in from the keyboard. If the mouse cursor is not positioned there, you will not be able to enter a name. Then click on Write.