VEGA On-line
VEGA Web Edition

 

1.0 Introduction

VEGA On-line is a Web server for all Internet users that want access to some molecular modelling applications everywhere without install any software package. The main features of the VEGA On-line server are:

 

1.1 Available services

The server provides some Web services:

All these services can be enabled or disabled in the configuration file.

 

1.1.1 VEGA WE

VEGA WE is a server-based service for all Internet users that want use the basic VEGA features without install it on their computer. It consists in two software components: the VEGA On-line Web server and the VEGA command line version. The  Web server sends the HTML main form to the user's Web browser. When the form is completed by the user and the Run VEGA button is pressed, the data is sent to the Web server trough the standard POST command. The server process internally the data, saving  the input molecule into a file and processing the user options. Thus, VEGA is launched and VEGA On-line wait the end of the calculation processing the output to be compatible with the HTML standard. Finally, the output is sent across the Net.

 

1.1.2 MolEdit

The MolEdit is small service that allows to draw a 2D structure thanks to the Molinspiration's JME applet, to perform a conversion to 3D (provided by AMMP molecular mechanics software) and to save it in any molecule format supported by VEGA. The edited molecule is read by VEGA that performs the following steps:

  1. if needed, add the hydrogens;
  2. assign the atom charges (Gasteiger - Marsili method);
  3. save the molecule in the AMMP file format.

AMMP optimizes the structure in two steps:

  1. distance geometry optimization by Gauss - Siedel algorithm (15 steps);
  2. conjugate gradients minimization (100 steps, toler = 0.01).

The minimized structure generated by AMMP is read by VEGA and converted to the file format requested by the user. Finally, it's sent to the user.
The optimization phase isn't completely exhaustive because 100 steps could be insufficient to optimize big molecules, but is enough for a rough 3D model.

 

1.1.3 Log kwIAM.MG/DD2 calculator

This Web service offers the possibility to predict the phospholipophilicity of all compounds included in PubChem collection as log kw of both MG and DD2 chromatographic columns. The prediction methods are based on experimental measures of log kwIAM.MG and log kwIAM.DD2 made by Francesco Barbato, Lucia Grumetto and Giacomo Russo of University of Naples Federico II.

The method used to predict both Log kwIAM.MG and Log kwIAM.DD2 is based on these equations:

Log kwIAM.MG = -0.1405 (± 0.1282) + 0.4401 (± 0.0297) miLogP + 0.0536 (± 0.0057)
Heavy_Atoms - 0.0833 (± 0.0201) HLBM - 0.0435 (± 0.0144) Rotatable_bonds

 

n = 204 r2 = 0.81 q2 = 0.80 SE = 0.438 F4,199 = 213.92 P < 1.0 10-8 PC = 39.403

 

Log kwIAM.DD2 = -2.3989 (± 0.2812) + 0.4936 (± 0.0379) miLogP + 0.4354 (± 0.0470)
Volume_Diameter - 0.0640 (± 0.0226) HLBPSA - 0.0497(± 0.0173) Rotatable_bond
s

n = 160 r2 = 0.85 q2 = 0.84 SE = 0.459 F4,155 = 212.94 P < 1.0 10-8 PC = 33.974

where:

miLogP is the log P predicted by the method developed by Molinspiration Chemoinformatics, Hravy_Atoms is the number of heavy atoms, HLBPSA is the hydrophilic-lipophilic balance calculated with the PSA method (see below), HLBM is the mean of the hydrophilic-lipophilic balance values predicted with three different methods (Griffin, Davies and PSA), Rotable_bonds is the number of rotatable dhiedral angles and Volume_diameter is the diameter length of a hypothetical sphere with the same volume of the molecule.

HLBPSA is defined by the following expression:

HLBPSA = 20 * PSA / Surface

where PSA is the polar surface area and Surface is the total surface.

The complete discussion of the method is available in Eur J Pharm Sci. 2016 Dec 2. pii: S0928-0987(16)30519-X (doi: 10.1016/j.ejps.2016.11.026).

These equations were implemented in this Web service that can predict Log kw values following these steps:

  1. The service connects itself to PubChem to search and download the 3D structure of the molecule specified by the user. PUG REST APIs are used to interface the service to PubChem.
  2. VEGA command line calculates the molecular descriptors (HLBs, number of rotatable dihedrals, volume  diameter) and  converts the structure to SMILES.
  3. The SMILES string is sent to Molinspiration Web service to retrieve miLogP. RESTful interface is used to get the property.
  4. Each property value is checked if it's in the range of values of the training set used to derive the QSAR models. If the property is outside of the prediction domain, a warning message is shown.
  5. Finally, Log kw values are calculated and shown in the page.

 

1.1.4 ProBuilder

The ProBuilder service builds a 3D peptide starting from its aminoacid sequence in raw or FASTA format. It applies the secondary structure specified by the user changing the backbone torsion angles (Phi, Psi and Omega). The peptide building, the hydrogens and the amino acid side chain adding is provided by VEGA. The molecule sent by the user is read by VEGA that provides the following steps:

  1. construction of the protein backbone;
  2. secondary structure change, applying the template specified by the user (alpha helix, left handed helix, 3.10 helix, p helix, beta strand, anti-parallel beta strand, parallel beta strand) or the Phi, Psi and Omega  torsion values;
  3. adding of amino acid side chains (optional);
  4. adding of hydrogens (optional);
  5. conversion of the resulting structure in the user-selected file format.

No structure optimization is performed and so a MM minimization of the output structure is required.

 

1.1.5 Virtual logP

The Virtual logP is obtained by the Molecular Lipophilicity Potential (MLP) that is calculated projecting the Broto-Moreau lipophilicity atomic constants on the molecular surface. Because the MLP is sensitive to conformational effects, the logP prediction requires a 3D structure with full hydrogens as input. For better results, the logP should be calculated for all most interesting conformations obtained by an exhaustive conformational analysis. The molecule sent by the user is read by VEGA that calculates the MLP and predicts the virtual logP. The output is converted to the HTML format and sent to the user browser.

For more information about the MLP and the Virtual logP, you can read the following paper:

P. Gaillard, P.A. Carrupt, B. Testa, A. Boudon, "Molecular Lipophilicity Potential, a tool in 3D QSAR: Method and applications", Journal of Computer-Aided Molecular Design, 1994, 8(2), 83-96.

 

1.1.6 PropKa On-line

Hui Li, Andrew D. Robertson and Jan H. Jensen developed a very fast empirical method for protein pKa prediction and rationalization (PROTEINS: Structure, Function and Bioinformatics 61:704-21, 2005). The desolvation effects and intra-protein interactions, which cause variations in pKa values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pKa sites. The Authors developed a program (PROPKA) to automatically predict pKa values based on these empirical relationships within a couple of seconds. Unusual pKa values at buried active sites, which are among the most interesting protein pKa values, are predicted very well with the empirical method.
With the kind permission of the Authors, the PROPKA executable is included in the VEGA ZZ package and now is accessible trough the VEGA On-line service. The user send the molecule to the server that automatically converts it to PDB 2.2 thanks to VEGA. The output is passed to PROPKA and its output is converted to the HTML format and sent to the user.

For more information about the method, you can read the following papers:

 

1.1.7 Score

The Score service allows to calculate some different docking scores of ligand-receptor complex that can be submitted as a whole file containing both interaction partners or as two separated files. The calculation phase is provided by VEGA and consists in the evaluation of the following scores/energies:

Scoring function Description
Broto Hydrophobic interaction calculated using the Broto's and Moreau's atomic constants.
Broto square distance Hydrophobic interaction in which the distance between interacting atom pairs is considered as square value.
Broto cube distance Hydrophobic interaction in which the distance between interacting atom pairs is considered as cube value.
Broto Fermi's equation Hydrophobic interaction in which the distance is evaluated by the Fermi's equation.
CHARMM R6-R12 R6-R12 non-bond interaction evaluated by CHARMM 22 force field provided by Accelrys. To perform this calculation, the parm.prm file must be copied in the ...\VEGA\Data\Parameters directory. This file is not included in the package for copyright reasons.
CHARMM 22 R6-R12 R6-R12 non-bond interaction evaluated by CHARMM 22 force field.
CHARMM 36 R6-R12 R6-R12 non-bond interaction evaluated by CHARMM 36 force field.
CVFF R6-R12 R6-R12 non-bond interaction evaluated by CVFF force field.
Electrostatic Electrostatic interaction.
Electrostatic distance dependent Distance-dependent electrostatic interaction.

The molecule/s sent by the user is read by VEGA that provides the following steps:

  1. if you sent two separated files, VEGA creates the complex keeping the original atom coordinates, otherwise if you sent a whole file, VEGA detects the molecules and if there are more than two molecules, it will consider as ligand the molecule number indicated in the specific field;
  2. atomic charges attribution (optional);
  3. evaluation of the scores selected by the user.

This service allows to download the results as XML file that contains the energy contributions of each atom and residue.

 

1.1.8 Picture Gallery

Picture Gallery is a simple database service useful to store the pictures that can be shown inside the Web browser as thumbnails or full-size images. The database is also used by the VEGA SE screen saver and can be managed in easy way thanks to the Web interface: you can add/edit/remove the pictures and add/remove the picture groups.

 

1.1.9 Molecule directory

This is not a real service, but it's an example of file repository with browsing capabilities in which are stored the molecules. It's based on the virtual file system implemented in the Web server. The user can change the virtual directory in the configuration file (see below).

 

1.1.10 VEGA manual

As the Molecule directory, this is not a service, but an implementation of the virtual file system without the browsing capability.

 

1.1.11 CMSimple - Content Management system

To access to the included CMS, you must connect to the following page:

http://myserver:myport/cms

where:

To modify the CMS, you must click on login and put the test password. More details about the CMS, can be found in the on-line manual. To make the CMS as default page instead of the VEGA On-line main page, you must rename the file _index.php to index.php in the home directory (usaully ...\VEGA ZZ\Data\VegaWE).

 

2.0 System requirements

To install and use VEGA On-line, you need:

 

3.0 Installation

VEGA On-line is included in the VEGA ZZ package but it's not installed using the standard setup: to enable its setup you must choose VEGA On-line service when the VEGA ZZ setup wizard is shown. Two versions are included: the former (VegaWE.exe) is a standard Windows application working with all Win32 releases (including Windows 9x) and the latter (VegaWEService.exe) is a Windows service working with Windows Vista/XP/2000/NT only. If a 64 bit operating system is detected (Windows XP, Windows Server 2003 and Windows Vista x64 editions), the 64 bit versions of the previous two executables are installed.
If you want enable the MolEdit service, the JME and Chemis3D applets must be installed:

 

3.1 Running VEGA On-line

To run the standard version of VEGA On-line compatible with all Windows versions, you must select VEGA ZZ -> VEGA On-line -> VEGA On-line. The Web server starts in background and an icon is installed in the tray area. Clicking on that icon, a menu is shown:

Item Description
Home page Open the Web browser showing the VEGA On-line home page. This capability is useful to test the correct configuration of the services.
Admin page Open the Web browser showing the VEGA On-line administrator page, requesting the user name and password set in the configuration file. This page allows to inspect the log files and to manage the picture database.
Edit config. Edit the XML configuration file.
About Show the copyright message.
Exit Close VEGA On-line.

VEGA On-line can also executed as Windows service: it must be installed selecting VEGA ZZ -> VEGA On-line -> VEGA On-line Service -> Install in the Start menu. To start the service, choose VEGA ZZ -> VEGA On-line -> VEGA On-line Service -> Start. Restarting the system, VEGA On-line is automatically executed as the other services. If you want stop the service, select VEGA ZZ -> VEGA On-line -> VEGA On-line Service -> Stop. Please remember that when you reboot the system, VEGA On-line is restarted.
To uninstall the service, choose VEGA ZZ -> VEGA On-line -> VEGA On-line Service -> Uninstall.

 

4.0 Web server configuration

To configure the VEGA On-line, you must edit the vegawe.xml file in the ...\VEGA ZZ\Config directory, selecting VEGA ZZ -> VEGA On-line -> Edit config. in the Start menu. The settings ate automatically reloaded when you save the configuration file.
The following scheme shows the meaning of each XML tag of the configuration file:

 

Configuration file

 

Description


<vegawe version="1.0">
     

Main tag:
- version -> Version number of the configuration file.


  <server port="80" maxconn="100">
 

Web server parameters:
- port -> TCP/IP port (default 80).
- maxconn -> maximum number of simultaneous connections.


    <cache expire="3600"/>
 

Cache parameters:
- expire -> time in seconds for the Web server cache expiration.


    <admin user="admin" password="admin"/>
 

Administrator account:
- user -> user name (default admin).
- password -> administrator password (default admin).


    <logflush>300</logflush>
 

Log file frequency in seconds for flush.


    <maxpostlen>4194304</maxpostlen>
 

Default maximum POST length in bytes. If the POST size data is greater than the specified value, the method is automatically rejected. 


    <outclean>3600</outclean>
 

Frequency in seconds to clean the output directory in which are stored the files generated as output by the services.


    <servername></servername>
  Name of the server. If it's empty or omitted, the current host name is used.

    <homedir></homedir>
 

Home directory (default C:\ProgramData\VEGA ZZ\Data\VegaWE).


    <dbdir></dbdir>
 

Database directory (default C:\ProgramData\VEGA ZZ\Databases).


    <logdir></logdir>
 

Log directory (default C:\ProgramData\VEGA ZZ\Data\Logs).


    <vegadir></vegadir>
 

VEGA home directory (default ...\VEGA ZZ).


    <defdoc>index.htm</defdoc>
  Default documents that are searched if an URL without a specific document is requested.
    ...
  The number of default documents is unlimited.

  </server>
 

End of Web server settings.


  <gallery enabled="1">
 

Picture gallery service:
- enabled -> enable (1) / disable (0) the service.


    <picture width="800" height="600"/>
  Picture parameters:
- width -> full size width.
- height -> full size height.

    <thumb width="128" height="96"/>
 

Thumbnail parameters:
- width -> thumbnail width.
- height -> thumbnail height.


    <index columns="5"/>
 

Thumbnail index parameters:
- columns -> number of columns used to show the thumbnails.


  </gallery>
 

End of picture gallery settings.


  <index enabled="1">
 

Home page settings:
- enabled -> enable (1) / disable (0) the home page service index.


  </index>
 

End of home page settings.


  <logkwiam enabled="1">
  LogKwIAM service:
- enabled -> enable (1) / disable (0) the service.

    <maxpostlen>256</maxpostlen>
  Maximum POST length in bytes. If the POST size is greater than the specified value, the method is automatically rejected.

    <timeout>20</timeout>
  Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.

  </logkwiam>
  End of LogkwIAM settings.

  <moledit enabled="1">
 

MolEdit service:
- enabled -> enable (1) / disable (0) the service.


    <maxpostlen>4096</maxpostlen>
 

Maximum POST length in bytes. If the POST size is greater than the specified value, the method is automatically rejected. You can change it on the basis of the computational power because it determines the size of the molecule to convert from 2D to 3D.


    <timeout>10</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.


  </moledit>
 

End of MolEdit settings.


  <probuilder enabled="1">
 

ProBuilder service:
- enabled -> enable (1) / disable (0) the service.


    <maxpostlen>1024</maxpostlen>
 

Maximum POST length in bytes. If the POST size is greater than the specified value, the method is automatically rejected. It means that the user can't build a peptide longer than the specified value.


    <timeout>20</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.


  </probuilder>
  End of ProBuilder settings.

  <propka enabled="1">
 

PropKa service:
- enabled -> enable (1) / disable (0) the service.


    <maxpostlen>1048576</maxpostlen>
 

Maximum POST length in bytes. If the POST size is greater than the specified value, the method is automatically rejected.


    <timeout>20</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.


  </propka>
  End of PropKa settings

  <score enabled="1">
  Score service:
- enabled -> enable (1) / disable (0) the service.
    <maxpostlen>1048576</maxpostlen>
 

Maximum POST length in bytes. If the POST size is greater than the specified value, the method is automatically rejected.

    <timeout>10</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.

  </propka>
  Endo of Score settings.

  <vega enabled="1">
 

VEGA WE service:
- enabled -> enable (1) / disable (0) the service.


    <maxdotdens>50</maxdotdens>
 

Maximum dot density in surface calculation. Increasing this value, it grows the possibility to create an overload situation.


    <maxpostlen>262144</maxpostlen>
 

Maximum POST length in bytes. If the POST size data is greater than the specified value, the method is automatically rejected.


    <timeout>10</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.


  </vega>
 

End of VEGA WE settings.


  <virtuallogp enabled="1">
 

Vistual logP service:
- enabled -> enable (1) / disable (0) the service.


    <maxpostlen>262144</maxpostlen>
 

Maximum POST length in bytes. If the POST size data is greater than the specified value, the method is automatically rejected.


    <timeout>10</timeout>
 

Service timeout in seconds: the service can't use more than the specified time to complete the operation. This is useful to avoid the server overload.


  </virtuallogp>
 

End of Virtual logP settings.


  <vdir alias="/manual" browse="0" user="all">
    %VEGADIR%/Docs/Html
  </vdir>
  Virtual file system - virtual directory:
- alias -> virtual path of the directory.
- browse -> enable (1) / disable (0, default) the directory browsing.
- user -> user name owner (all, none).
- Path of the directory in the local file system.
  ...
  The number of virtual directories is unlimited.

  <vfile alias="/VegaSE.exe" execute="0">
    %VEGADIR%/VegaSE.exe
  </vfile>
  Virtual  file system - virtual file:
- alias -> virtual path and file name.
- execute -> enable (1) / disable (0, default) if the program is executed as CGI.
- Full path and file name in the local file system.
  ...
  The number of virtual files is unlimited.

  <filemap ext="c" args='-run "%s"'>
    %VEGADIR%/Tcc/tcc.exe
  </filemap>
  Define a new file mapping that will be used by the CGI interface:
- ext -> file name extension to recognize the scripts that will be interpreted / compiled.
- args -> arguments that will be passed to the interpreter / compiler. The %s string is used to specify the full path and file name of the script.
- Full path and file name of the script interpreter / compiler
  ...
  The number of file mapping entries is unlimited. To enable/disable a script engine, you can add/remove its filemap entry.

  <mime type="text/html">htm html shtml</mime>
 

Mime types:
- type -> mime type.
- file name extensions.

  ...
 

The number of mime types is unlimited.


</vegawe>
 

End of the VEGA On-line configuration file.


You can use special directory names that are automatically expanded when the configuration file is loaded:

Variable Typical value Description
%BINDIR% C:\Program Files (x86)\VEGA ZZ\Bin\Win32 Directory of VEGA executables.
%CONFIGDIR% C:\ProgramData\VEGA ZZ\Config Configuration directory.
%DATADIR% C:\ProgramData\VEGA ZZ\Data Data directory.
%DBDIR% C:\ProgramData\VEGA ZZ\Data\Databases Directory of databases.
%HOMEDIR% C:\ProgramData\VEGA ZZ\Data\VegaWE Home directory.
%LOGDIR% C:\ProgramData\VEGA ZZ\Data\Logs Log directory.
%REBOLDIR% C:\Program Files (x86)\Rebol\View REBOL executable directory.
%VEGADIR% C:\Program Files (x86)\VEGA ZZ VEGA ZZ installation directory.
%WINDIR% C:\WINDOWS Windows directory.

 

5.0 Picture gallery update

The picture gallery can  be managed trough the Web interface. To do it, you must connect to the Web server using the following URL:

http://myserver:myport/admin

where:

When the dialog window is shown, put the administrator user name and password as in the admin tag of the configuration file. Click Image gallery and the Gallery administration page is shown. To add a new picture in the database, click Add a new picture, select the Picture file, put the Title, the Description, the Keywords and choose the picture Group. Click the Add button to upload and store the image in the database. The picture must be in JPEG or BMP format and it's automatically scaled to the resolution specified in the configuration file (see the picture tag in the gallery section). In the same way, the thumbnail is created with the size specified in the configuration file (see the thumb tag in the gallery section).
Clicking Edit the pictures in the gallery administration page, you can change the attributes and remove one or more pictures from the database. Checking the first column and clicking the Delete button at the at the table bottom, you remove one or more pictures. Clicking the thumbnails you can see the picture at full size and clicking the Title, you can update the picture an its attributes.

 

6.0 History

 

7.0 Copyright and disclaimers

All trademarks and software directly or indirectly referred in this document, are copyrighted from legal owners. VEGA, VEGA ZZ and VEGA On-line are freeware programs and the Authors accept no responsibility for hardware/software damages resulting from the use of these packages. No warranty is made about the software or its performance.

 

VEGA On-line
is a software developed in 2004-2017
by Alessandro Pedretti & Giulio Vistoli
All rights reserved.

Alessandro Pedretti
Dipartimento di Scienze Farmaceutiche
Università degli Studi di Milano
Via Mangiagalli, 25
I-20133 Milano - Italy
Tel. +39 02 503 19332
Fax. +39 02 503 19359
E-Mail: info@vegazz.net
WWW: http://www.vegazz.net

 

CMSimple
is a Content Management System developed in 2010-2017
by Peter Andreas Harteg
All rights reserved.

HARTEG IT
Peter Andreas Harteg
Knarregårdsvej 5
DK-3790 Hasle - Denmark
E-Mail: peter@harteg.dk
WWW: http://www.cmsimple.com

For more details about the CMSimple AGPL license, click here.