|ChemicaElectrica Gateway is intended to be a general purpose Chemistry program useful in the internet age. We have especially focused on making the program as flexible as possible by allowing the user to be able to modify almost everything. The program has four key components: a large database of molecules, user modifiable menus, substructure and similarity searching, and a 3-D drawing window.
For teachers and students we envision them linking the curriculum to the menus and icons, creating databases of the compounds, reactions and pathways covered in the lessons, and having the capability of linking it all to what is available on the internet.
For researchers we see them being able to do substructure searches of the database, then with one click bring up the molecules found in the search in vendor catalogs, Wikipedia pages or the web pages of the US government.
For people in the corporate world we see them linking the menus and user defined fields to memos, corporate web pages and tables of data about specific compounds and then having a way to do substructure search, similarity search and internet searches on the molecules found in the corporate databases.
For an investor in biopharmaceutical companies, they could search for competitor compounds and then quickly, with one click, do a Google search on all the matches, as well as search Medscape, C & E News and Wikipedia.
For the general public, they can locate compounds found on the labels of household products, get immediate information from the ChemicaElectrica database on the compounds and do an internet search via Google, Wikipedia, the US Government's web site and Medscape (or other site of the user's choosing) quickly.
Another goal is to make this program easy to use and intuitive -- so simple you will never guess the vast amount of work, spanning many years, that went into making it.
We encourage suggestions for improving this program.
So: on to an overview of the features of the program.
James Quinn (Ph.D.), program designer, Norgwyn Montgomery Software Inc.
North Wales, PA, USA
TABLE OF CONTENTS
2. Built in flexibility in the menus and icons
3. The database
a. Editing text in the database
b. User defined fields
c. Molecular Display - making beautiful pictures, and copying and printing them
d. Passwords and Security
4. Text search
5. Similarity search
6. Drawing molecules
What the buttons in the drawing window do
What the menus in the drawing window do
a. simple small molecules
b. complex rings
7. Substructure search
8. Energy minimization:.MM2 and MOPAC
9. Reaction database
10. Interaction with other programs - and how to connect your program to ChemicaElectrica Gateway
11. Product Support.
1. Installation and after you install the program.
If the program does not automatically start, run setup.exe (found on your CD) from the Windows start menu. If the program finds a newer version of a component of ChemicaElectrica already installed on your machine, keep the newer component that is already installed. ChemicaElectrica Gateway requires about 140 megabytes of disk space and runs on Windows 98, ME, 2000, XP, Vista, 7 and 8.
After the program has been loaded on your machine, open it and:
You will probably want to change the password.
You may want to customize the menus (see next section.)
You may want to learn how to draw a molecule.
To uninstall the program.
a. Go to your control panel, select Progams and Features and uninstall ChemicaElectrica. This removes most of the program AND uninstalls it from the Windows system registry.
b. After doing (a), delete the ChemicaElectrica directory.
2. Built in flexibility in the menus and icons
Adding other databases:
Databases should be in the ChemicaElectrica format or they will cause an error on loading. The ChemicaElectrica format is Microsoft Access with over 200 defined fields. The program expects these fields to have specific names. At present these databases can only be created with the program Molecular Modeling Pro Plus. or by making copies of Mydata.mdb or ChemicaElectrica.mdb.
If you have created databases in the ChemicaElectrica format then you can add them to the ChemicaElectrica Gateway File menu by going to the File menu and selecting "Add, Delete or Change items on this Menu." A window will appear which will help you do this. It will request that you give it the text for the menu, a file location, and whether you want it to be password protected and read only or not.
Adding/editing the More menu:
To add, delete or edit the More menu items, go to the More menu. Select "Add, Delete or Change this Menu." Supply your ChemicaElectrica password. A new window will pop up. You will supply the text for the menu item and the link. In addition there are a number of options.
- Checking add structural file to the command would cause a molfile to be saved and the program opens with the name of the molfile appended to the program name (e.g. c:\mmp\mmp32.exe c:\chemelectrica\temp.mol) so that the program opens with the molecule displayed.
- Checking "Google search of URL for current molecule" will perform a Google search of the URL for the molecule.
- "Add molecule name to end of URL" will do just that. (e.g. if you typed in the URL "http://www.google.com/search?q=" and checked this box with acetone displayed the program would open Internet Explorer with the URL http://www.google.com/search?q=acetone.
- Putting the molecule on the clipboard will give a menu item that when clicked will open a program and copy a molfile onto the Windows Clipboard.
Adding/editing the icons at the bottom right of the screen:
There is a detailed description of how to add or change the icons and links found at the bottom right of the Data Window HERE.
3. The databases
Note that this program cannot add or delete molecules from the databases. To do that you will need Molecular Modeling Pro Plus, a program sold separately. We are constantly adding new molecules to the database.
3a. Editing text in the database - Read Only versus Read and Write Access
There are two databases that come with this package: ChemicaElectrica.mdb and Mydata.mdb. At the beginning they are identical except that ChemicaElectrica cannot be edited (it is marked "Read Only".) This is so that if you get an update from us of ChemicaElectrica.mdb it will not erase all your changes. Mydata.mdb, on the other hand, can be changed to Read and Write access by going to the File menu and unselecting the menu item "Read Only." You will then be asked to supply your ChemicaElectrica password. All the fields in the database can then be edited (changed) simply by typing in something new. Changes occur to the database immediately and you do not need to save the changes - they are saved as soon as you type them.
If you reinstall the databases, the changes you make to mydata.mdb will be lost.
3b. User defined fields
A number of the fields in the databases are left blank and unnamed so you can create your own fields. You access these field by clicking the "User data" button found on the lower right side of the General tab.
A new series of tabs will appear (you can go back to the other tab series by clicking on the "Public data" button.) The field displayed on the "Numbers" and "Text" tabs should be given names if you intend to populate them with data. A button entitled "Add/Edit field names" near the bottom of the screen allows you to do this. To add field names and to edit data within the fields your database must be in Read and Write mode. To change from Read Only to Read and Write uncheck the Read Only button on the File menu and supply the ChemicaElectrica password when it appears.
Text Fields: You are given two "memo" fields and six "text" fields per molecule. Text fields are limited to 256 characters, while memo fields allow large blocks of text.
Picture fields: There are six fields on this tab per molecule. The data is the name of the jpeg or bitmap file. You can browse the file names by double clicking the text box. Hitting the Go button will display the picture. If the first text box has a file name the picture there will display automatically. We have started to attach 2-d structures to the first picture text box, but at the time of writing this are not very far along.
Numeric fields: These fields should first be given names with the "Add/edit field names" button. Numbers can be integers or single precision (from -3.4E38 to +3.4E38) floating point numbers.
Table fields: You are given six table fields (links to spreadsheets or tables) per molecule. If the file ends in .xls it will open the spreadsheet with Excel. Otherwise it will use Internet Explorer to open the default program associated with the file extension you provide.
Link fields: You are given ten link fields per molecule. These can be internet URLs or file names (to .doc, .txt files etc.)
3c. Molecular display - making beautiful pictures, and copying and printing them
The molecular display in ChemicaElectrica Gateway are 3-d rotatable drawings by default. Rotate the drawing by holding down the right mouse button and dragging the mouse. You can associate static 2-d drawings (links to windows bitmap files or JPEG files instead.
More beautiful rotatable drawings can be viewed by clicking on the red, green and blue molecule icon at the bottom right of the General tab. This brings the molecule up in the MMPviewer program. Make the molecular appear larger or smaller by holding down the Page Up or Page down button. Move the molecule left or right or up or down by clicking on it with the left mouse button and dragging it with the left button held down. Rotate the molecule by holding the right mouse button down and dragging the mouse.
The default display mode is shaded spheres. There are a number of other ways to view the molecule. For instance if you would like to see the wire frame embedded in translucent shaded spheres, go to the Display menu of MMPViewer and select combination and Wire Frame/Space Fill.
To save the image as a JPEG file simply go to the File menu and save it. You can then import the saved picture into any other program that can open a JPEG file. You can also print out the picture using the File menu including to large format printers.
3d. Passwords and Security
The ChemicaElectrica Gateway program comes with a password that is required to unlock certain features of the program. That password is typically your name in lower case letters. You should change this password soon after getting the program. You do this from the Options menu (select Change User Name or Password.) To access this feature you will have to know your password. If, for some reason, you do cannot find your initial password, you can contact us at email@example.com. Do not lose your password once you have changed it.
The two databases that come with this program are identical except that Chemelectrica.mdb is read only and mydata.mdb can be edited after changing it from "read only" to "read and write". To change the mydata.mdb to read and write, go to the File menu, select Read Only and give the program your password.
You will also need your ChemicaElectrica password to modify the menus and icons.
If you have a database that needs to be kept secret, give it a password when you create it using Molecular Modeling Pro. This password can be different than the one used by ChemicaElectrica Gateway and can be specific to the database. You should also store the structural information within the database instead of as external molfiles, as the external molfiles are easily read ASCII text files.
4. Text search of the database or internet
Type in the text and hit enter and the program will search the database's text fields for a match. Hitting the enter button is the same as hitting the Next button. Hitting the Find button finds the first match (and hitting it twice in a row is a bit pointless.) If you hit the "Internet" button to the right of the Next button it will do a Google search of the internet instead of searching the database. This is different than hitting the Google icon at the bottom of the Data Window because the Google icon only does a search of the compound by the name displayed at the top left.
5. Similarity search
Similarity searches can be done from the Data window or the Drawing window. The difference is that from the Data Window, the program searches for molecules structurally similar to the molecule currently displayed. When done from the Drawing Window it looks for molecules similar to any molecule you can imagine and draw in the Drawing Window.
In either case the search can be made more or less specific by use of the slider bar found adjacent to the Similarity button. Sliding the bar to the right will make the search less specific and find more hits.
Performing the similarity search brings up two new Windows: a) the Notepad window has statistics about the search and gives you a way of saving the results or printing them out; b) the list of hits in the ChemicaElectrica Similarity Window can be clicked on to go to the molecule of interest in the database. From there another click will open the data in Wikipedia, Google Search, or ChemID Plus.
The Similarity buttons are found at the bottom right of the Data Window and the top left of the Drawing Window.
The Similarity search works by counting the number of various substructural features of the two molecules being compared (like the number of amide groups, the longest path containing just carbon and nitrogen, the number of aromatic nitrogens, etc. - about 150 of these features altogether) and also compares some whole molecule features (like molecular weight and various connectivity indices.)
If you are interested in the actual numbers used they are stored in a database whose file extension is .ssf. For the ChemicaElectrica database this file is called ChemicaElectrica.ssf. This file is created by Molecular Modeling Pro. If you create your own database and its .ssf substructure file becomes corrupted, delete it, open Molecular Modeling Pro, open your database there, and try to do a substructure search from the Molecular Modeling Pro Database Window. This will recreate the .ssf file.
6. Drawing molecules
You probably want to go right to drawing a molecule. The little tutorial (should take about 10 minutes) can be found HERE. For a few extra details, below is a description about what every menu item and button on the Drawing Window does in alphabetical order.
Not on the menu or buttons, but important: a) To start a molecule, simply click in the middle of the screen. If you don't want carbon then click on the N, O, H, S, P, Cl, F, Br, I or Other button first, then click on the middle of the screen. If you want to draw a ring first, click on the Rings button first. b) To draw the second atom just click on the first atom. To draw the next atom just click on one of the previous two atoms. ChemicaElectrica will automatically add them with the correct bond lengths and angles (from the scientific literature.) c) Rotating the molecules is done by holding down the right mouse button and dragging it around. You can also get the molecule to rotate by hitting the x, y or z keys on your keyboard. Hit the "a" key to stop the rotations and put you back in drawing mode. d) a text message appears in a little blue box near the top of the screen that gives hints about what clicking on the screen will do next.
What the various buttons in the drawing window do:
+ Button: Click on this and then click on an atom: a positive formal charge +1 larger than before is placed on the atom.
- Button: Click on this and then click on an atom: a negative formal charge -1 less than before is placed on the atom.
0 (zero) button: Clicking on Change, then this zero button, then on two bonded atoms results in bond deletion.
1 button: Sets the bond mode to single bond. If you click on the Change button before clicking on this button then click on two bonded atoms you will change the bond between them to a single bond.
2 button: Sets the bond mode to double bond. The next atoms drawn will have double bonds until you select another bond type. If you click on the Change button before clicking on this button then click on two bonded atoms you will change the bond between them to a double bond. . If the valence for your atom types is exceeded the program may not let you do this unless you add a formal charge to the atoms using the "+" or "-" buttons.
3 button: Sets the bond mode to triple bond. The next atoms drawn will have double bonds until you select another bond type. If you click on the Change button before clicking on this button then click on two bonded atoms you will change the bond between them to a triple bond. If the valence for your atom types is exceeded the program may not let you do this unless you add a formal charge to the atoms using the "+" or "-" buttons.
ADD button (left): Clicking on this button puts you in atom addition mode. It negates the effects of the Delete and Change buttons. It also sets everything back to the default condition (if you are stuck in some process, this may get it to stop.)
AMINO button: Brings up a Window with button labeled with the three letter codes of the various amino acids. Clicking on one draws it to the screen. Check the box "Build Polypeptide" and the amino acids will be connected to each other as you click on the buttons, allowing you to create a fairly complicated molecule in seconds or minutes.
Br button (left): selects bromine
C button (left): selects carbon
CENTER button (upper row): Brings the molecule to the center of the screen. Use this button when the molecule grows too large.
CHANGE button (left): You can change the atom type (element) of something you have drawn by clicking on this button, then an atom type (i.e. click the C, H, N, O, P, S, Cl, Br, I, F or Other button) then clicking this button, then clicking on an atom you have drawn. You can change a bond type by clicking this Change button, then clicking on the 0, 1, 2 or 3 button, then clicking on the two atoms at either end of the bond. Clicking on Change and zero (0) and the two atoms will result in bond deletion.
CHEMSITE icon (green and yellow icon, upper right): If you have the program Chemsite or Chemsite Pro on your machine this will open it with the current molecule. This will give you additional capabilities: Amber minimization, molecular dynamics simulations, many impressive graphics options, ab-initio and DFT surface drawings and geometry optimization, crystal structure drawing, and 2-D drawing and more.
Cl button (left): selects chlorine
CLEAR button (lower left): Clears the drawing and all the information about every molecule on the screen, leaving it blank.
DELETE button (left area of screen): Click on this button then click on an atom. It will be deleted. Click on this button twice and you are given a choice of deleting a whole molecule (useful if you have more than one), all the hydrogens, or an atom.
GET CURRENT MOLECULE button (left): Clears the screen and imports the molecule displayed in the Data Window to the Drawing Window.
F button (left): Selects flourine. Hitting the letter F on your keyboard will do the same thing.
H button (left): Selects hydrogen. Hitting this button twice will give you the option of adding hydrogen to all atoms on the molecule (looks up the atomic valences and adds the number of hydrogens needed to fill the valence.)
I button (left): Selects iodine. Hitting the letter I on your keyboard will do the same thing.
Small molecules. Displays properties calculated from the structure displayed in the drawing window. Here is an example of the output of the program and the references for the mehtolds:
Calculation from ChemicaElectrica for 1233A 4/10/2013
Total Molecular Weight: 324.4172
Total Formula: C 18 H 28 O 5
-- Percent H: 8.699393
-- Percent C: 66.64198
-- Percent O: 24.65868
-- Van der Waals volume for all molecules: 197.058356204653 (cubic cm/mol)
-- Van der Waals Volume for all molecules: 327.22331959793 (cubic angstroms)
-- Van der Waals Volume (ABC method): 196.387652186875 (cubic cm/mol)
-- Van der Waals Volume (ABC method): 326.1096 (cubic angstroms)
-- Surface area for all molecules: 26.0388649332198 (cm^2/mol * 10 ^9)
-- Surface area: 418.539284585202 (square angstroms)
-- hydrophilic surface area = 14.3544082607059 cm^2/mol x10^9
-- % hydrophilic surface area = 21.9211914394761
Bioavilability calculations for 1233A (C 18 H 28 O 5 ):
Passed the Rule of Five for oral administration
Failed the Rule of Five for central nervous system bioavailability.
The compound is unlikely to be an effective drug for CNS applications.
-- Molecular Weight = 324.4172
-- Number of Hydrogen Bond Donors = 2
-- Number of Hydrogen Bond Acceptors = 5
-- Log P (Moriguchi) = 2.839606
-- Polar Surface Area = 94.72 Angstroms squared
-- ORAL BIOAVAILABILITY
-- Molecular weight is acceptable (<=500).
-- H Bond Donor number is acceptable (<5)
-- H Bond Acceptors number is acceptable (<=10)
-- LogP (Moriguchi) is acceptable (<=4.15).
-- CNS BIOAVAILABILITY
-- Molecular weight is acceptable (<=400).
-- H Bond Donor number is acceptable (<=3)
-- H Bond Acceptors number is acceptable (<=6)
-- Rule of Five failed due to high Polar Surface Area (>90 Angstroms square).
-- Components of Moriguchi Log P calculations
-- LogP (Moriguchi) parameter - (number of C and halogen)^0.6: 5.664525
-- LogP (Moriguchi) parameter - (number of N and O)^0.9: 4.2567
-- LogP (Moriguchi) parameter - number of unsaturated bonds: 4
-- LogP (Moriguchi) parameter - number of amphoteric structures: 0
-- LogP (Moriguchi) parameter - number of non-benzene rings: 1
-- LogP (Moriguchi) parameter - number of quaternary nitrogens: 0
-- LogP (Moriguchi) parameter - N and O proximity number: 4
-- LogP (Moriguchi) parameter - Internal Hydrogen bonds: 1
-- LogP (Moriguchi) parameter - Heteroatoms and groups on aromatic: 0
-- LogP (Moriguchi) parameter - Hydrocarbon indicator (0 or 1 unsaturation): 0
-- LogP (Moriguchi) parameter - number of Nitro groups: 0
-- LogP (Moriguchi) parameter - N=C=S and SC#N number: 0
-- LogP (Moriguchi) parameter - Beta lactam indicator: 0
Veber et.al. oral bioavailability model (J. Med. Chem. 45: 2615)
-- Passed the criteria for bioavailability of Veber et. al.
-- Polar surface area = 94.72 (should be <140 A squared)
-- Number of torsional bonds = 7.5 (should be <=10)
Potts & Guy (1992) log Kp skin permeation: -2.702825cm/h (calculated from Moriguchi log P and molecular weight)
Moss and Cronin (2002) log Kp skin permeation: -3.240888cm/h (calculated from Moriguchi log P and molecular weight)
Approximate log water solubility from categorization by rule of 5 parameters (Yamashita et.al.): -3.69
-- Rule of Five: C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Advanced Drug Delivery Reviews 23 (1997) 3-25
-- Moriguchi Log P: Moriguchi, L., S. Hinrono, Q. Liu, Y. Nakagome and Y. Matsushita (1992), Simple method of calculating octanol/water partition coefficient, Chem. Pharm. Bull. 40, 127-130
-- Moriguchi Log P: Moriguchi, L., S. Hinrono, Y. Nakagome and H. Hirano (1994), Comparison of log P values for drugs calculated by several methods, Chem. Pharm. Bull. 42, 976-978
-- Veber et. al. Bioavailability: Veber, D.F., S.R. Johnson, H-Y Cheng, B.R. Smith, K.W. Ward and K. D. Kopple (2002), J. Med. Chem. 45: 2615-2623
-- Potts & Guy Skin Permeation: Potts, R. O., and Guy, R. H. (1992). Predicting skin permeability. Pharm. Res. 9, 663669.
-- Moss & Cronin Skin Permeation: Moss, G.P., Cronin, M.T.D. (2002) QUantitative structure-permeability relationships for percutaneous absorption, re-analysis of steroid data. Int. J. Pharm. 238:105-109.
-- Water Solubility Decision Tree: F. Yamashita, T. Itoh, H. Hara & M. Hashida, Visualization of large-scale aqueous solubility data using a novel hierarchical data visualization technique, J. Chem. Inf. Model. 46:1054-1059 (2006)
-- Note: all the methods here were programmed by Norgwyn Montgomery Software Inc. and may vary from the values obtained with other programs. Results apply to organic molecules containing H, C, N, O, F, P, S, Cl, Br and I. Results do not apply to biopolymers.
-- Original VDW Volume and surface area: A. Bondi, J. Phys. Chem. 68(3):441-451 (see figure 3), with a proprietary method used for estimating triple overlaps
-- ABC method reference: Y.H. Zhao, M.H. Abraham, A.M. Zissimos, J. Org. Chem. 68(19): 7368-7373 (2003)
-- Hydrophilic surface area and Percent HSA are proprietary methods. See http://www.norgwyn.com/hsa.zip for a description.
Polymer properties. Here is an example of the output of the program:
Calculation from ChemicaElectrica for poloxamer 181 4/10/2013
Total Molecular Weight: 2024.733
Total Formula: C 102 H 206 O 37
-- Percent H: 10.25495
-- Percent C: 60.50778
-- Percent O: 29.23732
Polymer properties for (C 102 H 206 O 37 ):
-- number of backbone atoms (van Krevelen Z)= 109
-- Transition temperatures after D.W. van Krevelen, Properties of Polymers, 3rd ed., 1990
---- Glass transition temperature (C) = -24.6927
---- Melt transition temperature (C) = 285.183
-- van Krevelen and Hoftyzer's 3-D solubility parameters [(J^(1/2))/(cm^(3/2))]:
-- solubility parameter = 18.9032
-- dispersion = 16.6123
-- polarity = 1.32568
-- hydrogen bonding = 8.92205
-- molar volume (cm^3/mol) = 1821.54
-- Energy of Cohesion (J/mol)(Ref: van Krevelen) = 836207
-- Hoy's system (1985) for calculation of the 3-D solubility parameters [(J^(1/2))/(cm^(3/2))]:
-- molar attraction function (solubility parameter) = 19.9822
-- dispersion = 16.5248
-- polarity = 9.35547
-- hydrogen bonding = 6.22056
-- molecular aggregation number= 1.10731
-- Energy of cohesion (J/mol)(Ref: Hoy)= 676697
-- molar volume = 1837.05
-- Energy of cohesion (J/mol)(Ref: Fedors)= 628530
-- Molar Intrinsic Viscosity [g^(1/4)*cm^(3/2)/mol^(3/4)] = 259.2 (van Krevelen, page 251)
-- polymer water content (D.W. van Krevelyn, Properties of Polymers, 3rd ed., 1990, page 572)
-- polymer water content (30% relative humidity) = 0.9115301 moles
-- polymer water content (50% relative humidity) = 1.352547 moles
-- polymer water content (70% relative humidity) = 2.203367 moles
-- polymer water content (90% relative humidity) = 5.104591 moles
-- polymer water content (100% relative humidity) = 7.505104 moles
-- % polymer water content (30% relative humidity) = 0.8047278
-- % polymer water content (50% relative humidity) = 1.189441
-- % polymer water content (70% relative humidity) = 1.923269
-- % polymer water content (90% relative humidity) = 4.345631
-- % polymer water content (100% relative humidity) = 6.261275
-- van der Waal's volume= 1254.23523033634 (cubic cm/mol)
-- surface area = 168.652431674343 cm^2/mol x10^9
-- hydrophilic surface area = 90.8296706791682 cm^2/mol x10^9
-- % hydrophilic surface area = 53.8561287124246
Properties noted as from van Krevelen have the following reference:
'Properties of Polymers', 3rd edition, by D.W. van Krevelen, Elsevier, 1990
Hydrophilic surface area and Percent HSA are proprietary methods. See http://www.norgwyn.com/hsa.zip for description.
Connectivity indices and Graph Theory output and references:
Connectivity indices and graph theory results for abacavir (C 14 H 18 N 6 O 1 ) 4/10/2013 9:47:07 AM
Connectivity index 0 = 32.39698
Connectivity index 1 = 10.24152
Connectivity index 2 = 9.432055
Connectivity index 3 = 7.727338
Connectivity index 4 = 7.32709
Valence Connectivity index 0 = 29.60595
Valence Connectivity index 1 = 7.301056
Valence Connectivity index 2 = 5.80368
Valence Connectivity index 3 = 3.809708
Valence Connectivity index 4 = 3.255497
Difference index 0 = 2.791031
Difference index 1 = 2.940459
Difference index 2 = 3.628375
Difference index 3 = 3.91763
Difference index 4 = 4.071593
KAPPA shape index 2 = 5.893878
3-D Wiener number (0.5*sum of interatomic distances) = 3804.494
Milan Randic, JACS 97: 6609 (1975)
L. Kier, L. Hall, W. murray and M. Randic, J. Pharm. Sci. 64: 1971 (1975)
L. Kier and L. Hall, Recent Advance in Molecular Connectivity for Biological SAR Analyses (1984)
Lowell Hall, An Approach to Response Surface ptimization using Molecular Connectivity, hand-out from the Gordon Conference on QSAR.
L. Kier and L. Hall, Quant. Struct.-Act. Relat. 10:134 (1991)
Lemont Kier, QSAR in Durg Design and Toxicology, D. Hadzi and B. Jerman-Blazic eds., Elsevier, 1987. (kappa 2)
L. Kier, Quant. Struct.-Act. Relat. 4: 109 (1986) (kappa 2)
Nenad Trinajstic, Chemical Graph Theory 2nd ed., CRC Press, 1992
E state descriptors for the atoms in abacavir (C 14 H 18 N 6 O 1 )
N1: Intrinsic state value = 2; E State value = 2.011471
C2: Intrinsic state value = 1.667; E State value = 0.7498259
C3: Intrinsic state value = 2; E State value = 1.78331
C4: Intrinsic state value = 1.333; E State value = 0.1613048
C5: Intrinsic state value = 1.667; E State value = 0.7618552
N6: Intrinsic state value = 3; E State value = 4.349962
N7: Intrinsic state value = 3; E State value = 4.459397
C9: Intrinsic state value = 1.5; E State value = 0.8585066
C10: Intrinsic state value = 2; E State value = 2.091638
C12: Intrinsic state value = 1.667; E State value = 0.72251
C13: Intrinsic state value = 1.667; E State value = 0.2582577
C14: Intrinsic state value = 1.333; E State value = 0.203541
C17: Intrinsic state value = 2; E State value = 2.046126
N19: Intrinsic state value = 3; E State value = 4.274071
N20: Intrinsic state value = 2.5; E State value = 3.358519
N21: Intrinsic state value = 4; E State value = 5.839581
C22: Intrinsic state value = 1.5; E State value = 0.1719443
C26: Intrinsic state value = 1.333; E State value = 0.4832258
O29: Intrinsic state value = 6; E State value = 9.25717
C32: Intrinsic state value = 1.5; E State value = 1.162393
C33: Intrinsic state value = 1.5; E State value = 1.162393
Molecular electrotopological indices:
-- Sum of all atomic E-state values: 46.167
-- Maximum atomic E-state value: O29 9.25717
-- H bond donor E-state value sum: 18.45527
-- H bond acceptor E-state value sum: 33.55017
-- CH3R E-State value: 0
-- CH2RR E-State value: 3.355236
-- CHRRR E-State value: 0.8480716
-- CRRRR E-State value: 0
-- =CH2 E-state value: 0
-- =CHR non-aromatic E-State value: 4.137764
-- =CHR aromatic E-State value: 1.78331
-- =CRR non-aromatic E-State value: 0
-- =CRR aromatic E-State value: 2.492449
-- CHR triple bond E-State value: 0
-- CRR triple bond E-state value: 0
-- =C= E-State value: 0
-- NH2 E-State value: 5.839581
-- NHR non-aromatic E-State value: 3.358519
-- NHR aromatic E-State value: 0
-- NRR non-aromatic E-State value: 0
-- NRR aromatic E-state value: 2.011471
-- =NH E-State value: 0
-- =NR non-aromatic E-State value: 0
-- =NR aromatic E-State value: 13.08343
-- N triple bond E-State value: 0
-- N in nitro E-State value: 0
-- OH E-State value: 9.25717
-- ethereal O non-ring E-state value: 0
-- ethereal O in ring E-State value: 0
-- O double bonded: 0
-- F E-State value: 0
-- PRRR E-State value: 0
-- R=PRRR E-State value: 0
-- =S E-State value: 0
-- SHR E-State value: 0
-- SRR E-State value: 0
-- S=RRR E-State value: 0
-- S=R=RRR E-State value: 0
-- Cl E-State value: 0
-- Br E-State value: 0
-- I E-State value: 0
References for the electrotopological state values:
L. H. Hall, Brian Mohney and L. B. Kier (1991) “The Electrotopological State: Structure Information at the Atomic Level for Molecular Graphs”, J. Chem. Inf. Comput. Sci., 31: 76
L. H. Hall, Brian Mohney and L. B. Kier (1991) “The Electrotopological State: An Atom Index for QSAR, Quant. Struc-Act. Relat., 10: 43
Chemically Intuitive Molecular Index:
-- Eigenvalue 1: 3.24639779581762
-- Eigenvalue 2: 2.92174953824805
-- Eigenvalue 3: 2.82189278784819
-- Eigenvalue 4: 2.6398125492126
-- Eigenvalue 5: 2.50490570136767
-- Eigenvalue 6: 2.5007819760577
-- Eigenvalue 7: 2.39175261111022
-- Eigenvalue 8: 2.3126944647559
-- Eigenvalue 9: 2.00874202906554
-- Eigenvalue 10: 1.9516384640772
-- Eigenvalue 11: 1.94324846183066
-- Eigenvalue 12: 1.83912448288231
-- Eigenvalue 13: 1.63281127767796
-- Eigenvalue 14: 1.54058102726726
-- Eigenvalue 15: 1.16810417428782
-- Eigenvalue 16: 0.15
-- Eigenvalue 17: 1.66277191218146
-- Eigenvalue 18: 1.21511182091062
-- Eigenvalue 19: 1.76182074940956
-- Eigenvalue 20: 0.857354662625737
-- Eigenvalue 21: 2.18408566080271
-- Eigenvalue 22: 0.644786390449076
-- Eigenvalue 23: 0.781778225187214
-- Eigenvalue 24: 0.523890677154558
-- Eigenvalue 25: 0.251759401789709
-- Eigenvalue 26: 0.279542833516159
-- Eigenvalue 27: 0.674583178058842
-- Eigenvalue 28: 0.15
-- Eigenvalue 29: 1.52164882251329
-- Eigenvalue 30: 1.08123809026794
-- Eigenvalue 31: 0.15
-- Eigenvalue 32: 0.602051443416702
-- Eigenvalue 33: 0.300741028214917
-- Eigenvalue 34: 1.1016384640772
-- Eigenvalue 35: 0.428749033637552
-- Eigenvalue 36: 0.596774823670406
-- Eigenvalue 37: 0.15
-- Eigenvalue 38: 0.715242819195559
-- Eigenvalue 39: 0.15
Reference: Frank Burden, A Chemically Intuitive Molecular Index
Based on the Eigenvalues of a Modified Adjacency Matrix,
Quant. Struct.-Act.Relat. 16:309-314 (1997).
Balaban et.al. indices based on the molecular path counts
-- Q = 19929
-- S = 26.44114
-- D = 4.819843
-- A = 37.06532
-- P = 23.34108
Q = Quadratic molecular descriptor, Q = [sum(1 to j)p(i)^2]/(number of rings + 1), where p is the path count of each order i
S = [sum(1 to j) sqr(p(i))]/(number of rings + 1)
D = [sum(1 to j) sqr(p(i))]/(i*(number of rings + 1))
A = attenuated index = [sum(1 to j) p(i)]/(i*(number of rings + 1))
P = the path count index, = [sum(1 to j) p(i)]/(sqr(i)*(number of rings(i)+1))
path count of order 1 = 24
path count of order 2 = 35
path count of order 3 = 46
path count of order 4 = 64
path count of order 5 = 79
path count of order 6 = 95
path count of order 7 = 105
path count of order 8 = 120
path count of order 9 = 122
path count of order 10 = 111
path count of order 11 = 107
path count of order 12 = 88
path count of order 13 = 55
path count of order 14 = 30
path count of order 15 = 17
path count of order 16 = 15
path count of order 17 = 10
path count of order 18 = 2
number of rings = 4
Reference: A. T. Balaban, A. Beteringhe, T. Constantinescu, P. A Filip & O. Ivanciuc, Four New Topological Indices Based on the Molecular Path Code, J. Chem Inf. Model. 2007, 47: 716-731
MINIMIZE button (top): Use this button to change the geometry of your molecule to one that is more likely to exist at any given point in time. It uses Allinger's classical mechanics force field program MM2, a public domain program, to calculate the energy of the molecule. It uses a mathematical gradient method which iteratively finds lower energy states of the molecule until it can make no further improvement. You are given two options and they both have draw-backs. The first option is "Normal" MM2 which will find a local minimum. A local minimum is not necessarily the lowest energy conformation of the molecule, because if there are large barriers to bond rotation ("road-blocks" caused by an atom getting in the way) the MM2 program will not be able to rotate to the lowest energy state. The second option, "Global" MM2, finds the lowest energy state, but may change the stereochemistry of the molecule in doing it. The Global MM2 program breaks the molecule into fragments, minimizes them, then puts them back on with an analysis of the energy state, while rotating the connecting bonds 360 degrees. This Global MM2 program is not public domain and was developed by P. Baracic and M. Mackov.
MMPViewer icon (Red, green and blue icon, upper right): Opens up the high end graphics program distributed with ChemicaElectrica. This program displays shaded spheres, ball and stick, wire frames within translucent spheres, etc. Rotate molecules by holding the right mouse button down and dragging the mouse. Scale the molecules with the Page Up and Page Down keys. You can copy the graphics to the clipboard or print them out. The graphics are very fast because it uses the OpenGL (Open Graphics Library) to draw the molecules.
MOPAC button (version 6)(upper): Clicking this button will bring up a screen of options for the semi-empirical quantum mechanics program called MOPAC. This program, developed by James Stewart at the Air Force Academy and Michael Dewar and colleagues at the University of Texas, is in the public domain and you may distribute the MOPAC.exe file that comes with ChemicaElectrica free of charge. MOPAC is about as large as the rest of ChemicaElectrica Gateway and has a lot of features. A description of MOPAC in Wikipedia. The source code and manual for MOPAC version 6 is available on-line. ChemicaElectrica uses MOPAC to optimize geometry. If your molecule has a good starting geometry, then MOPAC will minimize it fairly reliably. If you suspect your molecule is in a high energy conformaiton (lots of overlapping atoms for instance, or an imported 2-D structure) you should minimize it with the MINIMIZE button first. If this doesn't work you can force MOPAC to do its calculations by selecting the GEO-OK option in the MOPAC Window. MOPAC also will perform a number of other calculations and will print them out in a Notepad window which can be saved or printed out. Among the things it always calculates are Heat of formation, ionization potential, dipole moment and atomic partial charges.
N button (left): Selects nitrogen. Hitting the letter N on your keyboard will do the same thing.
NEW MOL button (upper row): Start drawing another molecule without deleting the molecule on the screen. Allows you to draw more than one molecule (the limit is 60 molecules.)
O button (left): Selects oxygen.
OTHER button (left): Brings up the periodic table of the elements. Clicking on any element selects that element for drawing.
P button (left): Selects phosphorus. Hitting the P button on your keyboard will do the same thing.
PERSPECT button (upper row): Turns on and off a visual clue to whether an atom is close or far from the viewer. The closer the atom, the thicker the bond line is drawn when perspective is turned on. This feature is useful when you have stereochemistry to draw.
RINGS button (left): Brings up a list of rings, or alternatively you can create a generic ring of any size, with or without alternating double bonds. To draw a fused ring system not found in the list of rings, see the tutorial on Drawing complex rings.
S button (left): Selects sulfur. Hitting the S button on your keyboard will do the same thing.
SCALE button (upper row): Brings up a tool to make the molecule larger or smaller. It does not change the actual bond lengths and atomic radii - just changes the way the molecule is drawn. Hitting the "<" or ">" on your keyboard will do something similar.
SPACE button (upper row): If you have more than one molecule, this button will cause them to separate and be spaced evenly apart.
SIMILAR button (left): Compares the structure of the molecule drawn to all the molecules in the database and returns the most similar ones in a list. The slider just below the button returns a less specific search as you slide it to the right. More can be found HERE.
SUBSTRUCTURE SEARCH button (upper left): Draw in a molecule. Clicking this button will then find every molecule in the database that contains the structure you have drawn. The results will be found in a list. Clicking on a molecule name in this list will display that molecule in the Data Window. From there you can bring up the Wikipedia article, do a Google search, search catalogs, Medscape or bring the molecule up in Chemsite or Molecular Modeling Pro. The goal is make the internet searchable by substructure...
TRANSLATE button (upper row): This is for moving the atom up or down or left or right. Hit this button then drag the molecule around with the left mouse button held down.
Z90 button (upper row): This button will cause the molecule to rotate 90 degrees clockwise.
What the menus in the drawing windows do:
New: Clears the current molecule(s) from the screen.
Open: Opens a connection table file from the local computer. Formats supported include MDL Molfile, Macromodel file (Columbia University's modeling program, file format circa 1995) and Brookhaven pdb file. Connection tables are the way the structural information about a molecule are stored.
Save: Saves the current molecule as a connection table file or a picture. Connection file formats include MDL Molfile (version 2000), Macromodel file or Brookhaven pdb file (writes only hetatom format, though the program reads most of the other information when opening a file.)
Close: closes the drawing window.
Undo: allows you to undo minimizations and rotations.
Copy MDL Molfile to the clipboard: Puts an MDL Molfile on the Windows text clipboard for other programs to use.
Copy graphics to the clipboard: Puts a picture on the Windows clipboard for other programs to use.
Paste an MDL Molfile from the clipboard: Pastes a structure from another program into ChemicaElectrica's drawing window.
Name the molecule: Type in a name that will be saved with the molecule.
Font: Changes the font used by the Drawing window.
Set background color: Allows the user to choose a different background color than the black default.
Set text color: Allows the user to choose a different color than yellow for the text in the drawing window.
Color molecule by charge: The most positive atoms are colored blue, somewhat positive atoms are green, neutral atoms are white, somewhat negative are yellow and most negative are colored red. The program uses the MOPAC charges, if they have been calculated. Otherwise, it uses Del Re's method of calculating partial atomic charges.
Color molecule by lipophilicity: The most lipophilic atoms are colored dark blue, somewhat lipophilic are light blue, neutral atoms are colored white, somewhat hydrophliic are bright red and most hydrophilice are dark red.
Restore Molecule colors: Restores the atoms to the default colors: C = green, H = white, N = blue, O = red, F = light blue, Si an even lighter blue, P is magenta, S is yellow, Cl = yellow green, Br is brown, I is purple, metals are gray, Na, K, Li are white, etc.
Set atom color: Allows the user to choose what color an atom type will be.
Rotate bond: Select item. Click on the two atoms that define the axis of rotation. All the atoms in the groups attached to the second atom clicked on will rotate the specified amount.
Invert: After selecting this menu item, you can click on an atom to invert a stereocenter, thus changing the stereoisomer.
Mirror: Creates the mirror image of the molecule. If you have one stereocenter in a molecule, this will change the molecule to the other stereoisomer.
Set bond lengths and angles:
Change bond length: Select menu item, click on the two atoms and type in the new bond length in angstroms.
Change bond angle: Select menu item, click on three atoms and type in the new bond angle.
Change torsional bond angle: Select menu item, click on the two atoms that define the axis of rotation and the atoms attached to the second atom will rotate to the torsional angle that you type in.
Place atom at origin: After selecting this menu item, click on an atom to move to the center of the screen (the rest of the molecule will move with it.)
Move atom to the x axis: This rotates the molecule so that the atom that you click on is 180 degrees right of the center point.
Orient an atom the x-y plane: The rotates the molecule around the x axis, so that the atom you click on is in the x-y plane (i.e. its z coordinate value is near zero.)
Move an atom: After selecting this menu item, hold down the left mouse button on the atom you want to move and drag it with the mouse to the new location. This is way to change stereochemistry in a complex ring.
Info: Displays the molecular weight and molecular formula for the currently drawn molecule or molecules.
ChemicaElectrica Help: Brings up the main Help file which includes descriptions of all the buttons, menus and functions of the drawing window. The Help windows require Internet Explorer to be installed on your system.
Molecule drawing tutorial: Brings up the tutorial on drawing a molecule.
Drawing complex rings: Brings up the tutorial on drawing complex ring systems.
6a. Drawing simple small molecules
There is a little tutorial on drawing the molecule myclobutanil which you can find HERE. It explains enough to get you started.
6b. Drawing complex rings
A tutorial on drawing the tetracycline and sirolimus ring systems can be found HERE.
6c. Drawing polypeptides
To build polypeptides, click on the Amino button. Check the Build Polypeptide box. This tool will start at the N terminus. Just click on the buttons displaying the amino acid 3 letter code to add an amino acid to the polypeptide. If you own Chemsite, you may want to learn how to use its polypeptide builder as an alternative. The Amber force field in Chemsite was originally designed to work with polypeptides.
7. Substructure search
Draw in the molecule then hit the substructure search button. A list of all the molecules in the database containing the substructure you have drawn will appear. Clicking on a molecule name on the list will cause the molecule to appear in the Data Window. From there you can search the internet for information using the icon buttons at the bottom of the General tab.
ChemicaElectrica does take into account hydrogens you leave on the molecule. If you want to consider all possible substituents on an atom leave the hydrogens off it. If you want to only see R-C6H5-NH2 (para), then draw the 2 hydrogens on the para amine, otherwise you will also get R-C6H5-N(R)R where R is any group.
8. Energy minimization:.MM2 and MOPAC
The MINIMIZE and MOPAC buttons found at the upper right of the Drawing Window will improve the 3-D geometry of the molecules you draw. MM2 and MOPAC will optimize the bond angles and bond lengths and minimize atom-atom overlap. The MINIMIZE button uses the MM2 classical mechanics force field to minimize the energy of the molecule.
MM2 is a classical mechanics program developed by Norman Allinger to reproduce the equilibrium covalent geometry of molecules as precisely as possible. It has a look up table of optimum bond lengths and bond angles of various 2, 3 and 4 atom groups. If you draw a molecule not in the look up table ChemicaElectrica will tell you so and the MM2 routine will not run. You are given two options and they both have strengths and weaknesses. The first option is "Normal" MM2 which will find a local minimum. A local minimum is not necessarily the lowest energy conformation of the molecule, because if there are large barriers to bond rotation ("road-blocks" caused by an atom getting in the way) the MM2 program will not be able to rotate to the lowest energy state. The second option, "Global" MM2, finds the lowest energy state, but may change the stereochemistry of the molecule in doing it. The Global MM2 program breaks the molecule into fragments, minimizes them, then puts them back on with an analysis of the energy state, while rotating the connecting bonds 360 degrees. This Global MM2 program is not public domain and was developed by P. Baracic and M. Mackov.
MOPAC is a semi-empirical quantum mechanics program developed by James Stewart at the US Air Force Academy and Michael Dewar and colleagues at the University of Texas. MOPAC is about as large as the rest of ChemicaElectrica Gateway and has a lot of features. The source code and manual for MOPAC version 6 is available on-line. ChemicaElectrica uses MOPAC to optimize geometry. If your molecule has a good starting geometry, then MOPAC will minimize it fairly reliably. If you suspect your molecule is in a high energy conformaiton (lots of overlapping atoms for instance, or an imported 2-D structure) you should minimize it with the MINIMIZE button first. If this doesn't work you can force MOPAC to do its calculations by selecting the GEO-OK option in the MOPAC Window. MOPAC also will perform a number of other calculations and will print them out in a Notepad window which can be saved or printed out. Among the things it always calculates are Heat of formation, ionization potential, dipole moment and atomic partial charges.
9. Reaction database
The reaction database is reached from the Data Window's More menu (select "Reactions and Pathways".) At the time of writing this database is rather small. You can add to it by doing the following:
a) You can either supply a drawing saved as a JPEG or Window bitmap (.bmp) file OR alternatively you can supply an internet URL.
b) You do this by going to the "More" menu and selecting "Add Reactions and Pathways." Fill in the name of the reaction, a brief description of the reaction and the link the file containing your picture or a link to the URL of your web page.
If you would like to contribute your reaction pictures for inclusion in the next update of ChemicaElectrica Gateway, e-mail them to firstname.lastname@example.org.
10. Interaction with other programs and how to connect your program to ChemicaElectrica Gateway
There are numerous ways to connect your program or website to ChemicaElectrica Gateway.
ChemicaElectrica Gateway uses the old fashioned Shell method that dates from MS-DOS to open other programs. Shell has since the early days been incorporated in the Windows operating system (and thus still works.)
Your program then should be able to read the items on the Shell command line that come after your program OR your program should look for a molfile on the clipboard when it opens. ChemicaElectrica can put one of three things on the command line:
- a file location (could be a molfile, a document, a spreadsheet etc.)
- the molecule name
- a CAS Registry number
For more information on modifying ChemicaElectrica's menus and icons so they can call your program, see the section on flexibility.
ChemicaElectrica Gateway uses Internet Explorer to open web pages and non-program files. Internet Explorer has the capability of opening the appropriate program based on the file extension of the files you want to open. See the section on flexibility to see how to call Internet Explorer. Notice that if you want to open files specific to a particular compound you can do this with the "User Data" tab called Tables and Links.
11. Product Support.
This manual is displayed by Internet Explorer. Please use the search function of IE (control F) to search this long web page for your answer. If you find a bug or really get stuck, e-mail me at email@example.com (it will reach me, James Quinn). Please include your serial number (found in the Help menu/about box.)