The full WHAT IF provides more than 2000 options to the user. A few options only work on only one or a few of the aforementioned machines because that machine provides some special hardware features which the others do not have.
WHAT IF allows the molecular engineer to sit in front of a computer terminal or better, a graphics workstation, and ask questions that start with "What if ...." and then continue for example with "...I mutated that valine into an isoleucine?". The program can help the user by calculating the consequences of such a mutation. To do so it can use a three dimensional relational protein database in one, two, or three dimensions. It allows for quick evaluations of mutations in terms of occupied space, Van der Waals contacts, hydrogen bridges, accessible surfaces etc. The very fast access to the graphics system stimulates human inspection of results. The program is set up in a very transparent way, using many easy to use menu's. The user only needs to know the very few basic options, plus the options he or she wants to use. So, although WHAT IF offers more than two thousand options to the user, one only needs to know very few of those in order to answer even elaborate questions.
A graphics device can be used to continuously monitor answers to questions. Contacts, hydrogen bonds, salt bridges, accessible surfaces, etc. can be shown easily and quickly. The usage of a graphics device allows for interactive manipulation of structures. Structures can be shown with respect to one or more maps (eg. potential energy maps, or electron density maps). The option to color atoms or residues as function of their properties (like temperature factor, atom type, residue type, charge, hydrophobic moment, etc) facilitates quick evaluation of these properties.
The WHAT IF writeup is regularly updated on a World Wide Web (WWW) server. The URL of the WHAT IF homepage is:
http://swift.EMBL-Heidelberg.DE/whatif/This homepage does not use any fancy WWW tools, and can be read by all known versions of Mosaic, Netscape, etc. The program can at all times generate plot files. These can be postscript files, HP-plot files or just general files with draws and moves in it. In case a laser printer and the postscript software are present, WHAT IF can put screen pictures immediately at the laser printer in postscript format; either in black and white, or in color. The orientation matrix, scale factor, translation and slab-value (=clipping value) provided by the graphics system will be passed on to the general plot files.
The enormous flexibility of WHAT IF guarantees that new options can be added quickly and easily.
WHAT IF uses much less memory than comparable programs. Its memory requirements are very machine dependent. On all machines a swap file of 40 Mbyte is for all practical purposes adequate. For several machines we know the minimal and optimal memory requirements. These are listed below. Be aware however, that the same program normally requires more memory after an update of the operating systems. The only reason that operating systems are updated is according to me that they can make them bigger so that you need to buy more memory -).
Memory (in Mbytes)
Machine Operating system Minimal Optimal
DEC Ultrix ? ?
DEC Alpha OSF 2.* 64 64 *1
SG IRIX 4.* 16 48
SG IRIX 5.* 32 64 *2
IBM-Pc (clone) DOS 12 16
IBM-Pc (clone) LINUX 8 16
1) See chapter 96 for notes on swap-file usage.
2) Some WHAT IF users have experienced problems with WHAT IF on SG Indys with 32 Mbytes of memory and operating system 5.1 or 5.2.
The disk requirements are less humble. All databases together will occupy 140 megabytes. However, not all databases need to be present on disk at the same time, and the software to (re-)generate the databases at any desired size is part of WHAT IF.
If this is the first time you use WHAT IF for a certain project, you should create a new subdirectory.
IMPORTANT. KEEP EVERY PROJECT IN ITS OWN SUBDIRECTORY!WHAT IF starts directly after typing whatif. Be aware that WHAT IF takes up to two minutes on IBM-Pc (clones) under MS/DOS. Thereafter you are all set to go.
On UNIX machines your WHAT IF manager normally has defined a logical called `whatif`. If not try typing /usr/people/vriend/DO_WHATIF.COM
When ready, a menu and the WHAT IF prompt:
WHAT IF>will appear at the screen. This means that the program is ready to receive your commands. Whenever you see this prompt, you can get a list of options available at that moment by hitting the return key. The options show up at the screen in an order the logic of which will only become clear to you after you worked with the program for a couple of times. If you want to know what a certain option does, you can either type:
HELP OPTIONin which OPTION stands for the option of your choice, or look in the chapter in the paper copy or computer-readable copy of this writeup that has the same name as the menu you are in, or just use the alphabetical index.
The command SHORT will cause WHAT IF to show you all options available in this menu with a one line explanation for that option.
The command INFO can in most menus be used to get very extensive HELP on a topic. INFO uses the same syntax as HELP. And if no INFO pages are found, INFO will do the same as HELP
The most important thing to do is:
Go through the TUTORIAL!!!!!That takes a day or three, but you win that back in less than no time. You can also visit us at the EMBL for a one week user course.
In some menus you will find the command MORE. The execution of this command will add new options to this menu, Normally only the most used options are directly visible. That is done in order not to overload the user with options. MORE can not be undone. MORE only needs to be executed once per menu.
In several menus there are even more commands available after you typed MORE. If you type HIDDEN you get a short list of hidden commands in about ten menus. These commands are normally not documented further than by the text supplied by the HIDDEN command.
For the experienced user the possibility is build in to use most commands from every menu. To do so, you need to know the command's name, be able to use it without help, and to understand the way WHAT IF works. You activate this possibility by starting the command line with a percent sign. E.g. %SHOSOU will execute the soup menu command SHOSOU no matter in which menu you are.
Whenever you have activated an option which requires additional user input, you can cancel the option by typing 0 (zero) as answer to any of the follow-up questions. If zero is not acceptable to WHAT IF, it will tell you so; do not worry because there will come more questions, and at least one of them allows you to enter 0 (zero) to bail out. This always applies when you are prompted for a file name, for a residue, for a residue range, for a group, or for a row. In case you are prompted for something else, try 0 (zero) as input, there is no way that this can crash the program.
Commands that are related to usage of families are easily recognized because they have the three letter combination FAM in their name. The CLUFAM option brings you in the menu that deals with families and clusters.
Whenever you are prompted for one or more ranges you can also enter a family name.
Commands that are related to usage of clusters are easily recognized because they have the three letter combination CLU in their name. The CLUFAM option brings you in the menu that deals with families and clusters.
Whenever you are prompted for multiple ranges you can also enter a cluster name.
If you use type ahead, always give the first AND the last residue of any range, also if the first and the last residue are the same.
AA Amino Acid (Often also used for DNA/RNA...) AAS Amino Acid Sidechain (Often also used for DNA/RNA...) ACC Has to do with ACCessibility ALI ALIgnment ANA ANAlyse AND Logical AND operation ATM AToM BAD BAD (is not good) BFT B-FacTor BLD BuiLD (mainly protein) BND BoND between atoms CAV CAVity CEL Crystallographic CELl CEN CENter CHK CHecK CHI Torsion angle CLU CLUster of 3D related residues COL COLour CON CONtact COR CORrect CPK Solid spheres CYS CYSteine or cysteine bridge DBL DouBLe DEB DEBump, remove bumps DEF DEFault or DEFine DEL DELete or remove DG Distance Geometry rotamer and loop search DIF DIFference DNA DNA (or RNA!) DST DiSTance EDT EDiT ENV ENVironment, molecules to be taken into account ETM Energy TErm EVA EVAluate FAM FAMily, range of covalently connected residues FLP FLiP, or turn around FPO Phi-psi-omega, backbone torsion angles GET Read from a formatted file (see MAK, SAV, RES) GRA GRAphics GRL Superpose all frames/hits/etc. in one MOL-item GRI GRIn and grid GRO GROmos GRP GRouP of database hits H2O Water HBO Hydrogen BOnd HEL HELix HID HIDden (as in hidden, or invisible options) HIT HIT as in a hit in a database search HSP HSsP (multiple sequence alignment files) HST Helix, Strand, Turn (in other words: secondary structure) HYD HYDrogens INI INItializes something. INV INVerse (normally used for TRUE <--> FALSE inversions) LAB LABel (not picked label, but label in MOL-item) LIN LINe LOG LOGfile in which options/commands/results are written MAK Write in a formatted file (see GET, SAV, RES) MAP 3D electron density, property or probability distribution MAP MAT MATrix MLS MoLeculeS (see MOL) MOL MOLecule (unless MOL-object is meant) (see MLS) MOM MOMent as in hydrophobic MOMent MUT MUTate NAM NAMe NEU NEUral net NEW Replace something by an improved copy NMR Nuclear Magnetic Resonance OPT OPTimize (sometimes OPTionally...) OR Logical OR operation PCK PiCKed labels PAR PARameters PAS PASte PCT PerCenT PHI Backbone torsion angle PHI PRF PReFerred or PReFerence or PRoFile PRP PRoPerty (sometimes PRePare) PSI Backbone torsion angle PSI QUA QUAlity op packing REF REFine (=regularize) a protein structure RES REStore results from a WHAT IF specific file (see SAV, MAK, GET) RNG RaNGe of residues ROT ROTamer SAV SAVe results in a WHAT IF specific file (see RES, MAK, GET) SCN SCAN3D; relational structure sequence database SDB Show something from the DataBase SHL SHelL SEQ SEQuence (see SQS) SET Calculates something, without showing the results SHO Lists results, and displays them if applicable SMC SyMmetry Contact SML SMalL SOU SOUp (all WHAT IF's data) SPC SPeCial SPH SPHere in space SQS SeQuenceS (see SEQ) SRF SuRFace STA STAtus STS STatisticS SUP SUPerposition SYM SYMmetry TAB TABles (internal molecular spread sheet) TRA TRAjectory (sometimes TRAnslate) TST TeST USE USE or activate or incorporate VAC VACuum VAL VALue VDD Van der Waals (surface) VDW Van der Waals (radii) VOL VOLume WAL What if ALignment WAT WATer ZON ZONe of residues (see ZNS) ZNS Multiple ZoNeS (see ZON)
MOL-items are grouped in MOL-objects. A MOL-object can hold many MOL-items. If you do not use too many different colors per MOL-item, then an object can easily hold 20 of them (89 on S.G. machines). This might sound rather limited, but don't worry, I still have to meet the first user who managed to run into overflow problems while creating pictures at the screen.
SETICO 29 1Be aware however that several options will not (yet) treat the protons correctly yet, and some options will even create a stack-dump if used with the proton option active.
The protonisation is expected to be finished by mid 1996.
It is also possible to change parameters that are needed by the general commands. This can be done by typing SETPAR. This brings you in a menu which has many sub-menu's in it. All these sub-menu's allow for the changing of a group of parameters that logically belong together (eg all parameters that influence the way accessibilities are being calculated, or 3-D fragment database parameters, etc).
- A clicker-dee-click user interface that requires virtually no typing. - Completely automatic mutant prediction module. - Interactive torsion angle motion for all angles, not only side-chain. - Adding co-factors from the PDB files to WHAT IF's database. - User defined program lay-out. E.g. Menu color, window size, etc. will be read from a user edit-able parameter file. - Some small molecule operations will be added. - An extensive protein structure verification module will be added. etc.Users who plan to make large extensions to WHAT IF are urged to contact me first. I can then tell them if their plans are already being implemented by somebody else. This might save many weeks of programming efforts. To start programming one of the above options is of course certainly a waist of time because in less than half a year time they will be available.
Sorry for this, but it is just Rob and me doing every day programming, and not a team of ten or twenty scientists and programmers as for some of the extremely expensive just as much bugged commercial programs.
ACCESS Van der Waals and accessible surface options. ANACON Analysis, evaluation and visualization of contacts. ANATRA Analysis of Molecular Dynamics trajectories. BUILD Building proteins, adding residues. CHIANG Torsion angle evaluation, manipulation, analysis. CHKMDF Evaluation of (H,K,L,F,sigma) files. CHECK To check protein structures COLOUR Coloring atoms residues molecules, objects. CONOLY Interface to Connolly's programs. CLUFAM To group residues in 3D. DGLOOP Structure fragment database. DRUG A few options to manipulate small molecules. GRAEXT Special graphics. Arrows, ball and stick models etc. GRAFIC General 3D graphics menu. GRATWO 2D Graphics menu. (Phi-Psi plot, B-factor plot, etc.) GRID Interface to Goodford's GRID program. GROMOS Interface to GROMOS. HBONDS Hydrogen bond determination, evaluation and display. HSSP Interface to HSSP program (mutability prediction). ITMADM To manipulate graphical objects. LABEL Labeling atoms, residues, etc. MAP Administration and display of maps. MASMAP Manipulation, editing of maps. MAPEDT Crystallographic electron density envelop editor. NEURAL Activates a toy neural network. NMR NMR related commands. NOTES Is a protein specific notebook. PIRPSQ Sequence options (alignment, model by homology etc.) PLOTIT Plot options. PORNO To do molecular pornography (=really beautiful pictures) QUALTY Structure quality evaluation, mutant prediction. REFINE Structure regularisation. SCAN3D Relational protein structure database handler. SCNSTS Does statistics on relational database query results. SEARCH Interactive search for structure characteristics. SETPAR Parameter (re-)setting. SOUP Molecular administration (read/write/delete). STEREO Switch several stereo modes on/off. SUPPOS Superposition of molecules, residues, fragments. SYMTRY Symmetry matrix administration/application. TABLES Spread sheet for atomic data. WALIGN Multi sequence alignment. WATER Manipulation of water molecules. XRAY Holds a few Xray specific options. 3SSP Automatic multiple structure superposition.