| Can I submit jobs in background and continue to do other work? |
| Yes, users can submit jobs in background in VLifeMDS. The status, start time, end time, details of the submitted job can be verified in Task Manager. |
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| How to return to normal view mode after I open full screen? |
| Users can either click Esc from keyboard or right click on the mouse and select Normal View from the menu to return to normal view. |
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| What are the system requirements for using VLifeMDS? |
| Operating systems: |
Windows® XP, Windows Vista®, Windows 7, Linux (Fedora, Ubuntu, CentOS) |
| Recommended hardware: |
Minimum free hard disk space: 1 GB
Minimum required memory: 2 GB |
| Graphic cards: |
Standard graphic card (supporting OpenGL) |
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| How can I save molecule as a group or as a template? |
| VLifeMDS provides a facility to save user-specific atomic groups, which are used frequently. This feature enables the user to add a customized group to a ‘Group Class’. VLifeMDS also provides a facility using which a user can build a customized template for combinatorial library design. |
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| How can I select multiple columns and rows in a worksheet? |
| Users can use the shift key to select multiple rows and column. |
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| Can I run my jobs in a batch mode? |
| Yes. Users can optimize the molecules using Batch Optimize and dock ligands using Batch docking functions. |
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| How can I insert activity file in the worksheet while doing 2D and 3D QSAR? |
| Users can add a column in the worksheet and can insert activity from the experimental data corresponding to each molecule and save the file as .col2. User can import the saved .col2 file as and when the particular file is required. |
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| Which are the file formats that VLifeMDS supports in QSAR worksheet? |
| Worksheet scans for existence of VLifeMDS standard files "*.mds" and "*.mol2". If both file types are present first .mds and then .mol2 file format will open. |
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| What are the types of molecular descriptors? |
Following are some types of molecular descriptors:
- Topological Index
- Connectivity Index
- Center of Mass
- Radius of Gyration
- Moment of Inertia
- Wiener Index
- Balban Index
- Centric Index
- Hosaya Index
- Information Based Indices
- xlogP
- Hydrophobicity
- Element Count
- Path Count
- Chain Count
- Cluster/ Path cluster Count
- Molecular Connectivity Index
- Valence Molecular Connectivity Index
- Molecular connectivity Index of Chain fragment
- Valence Molecular connectivity Index of chain fragment
- Molecular connectivity Index of cluster/ path cluster
- Valence Molecular connectivity Index of chiV3cluster/ chiV4pathcluster
- Kappa Values
- Electrotopological atom_type count
- Electrotopological State Indices
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| Where will I get VLife software QSAR descriptor definations? |
| For descriptor defination click here.... |
| How can I specify dependency of the calculated descriptors in the worksheet while building a QSAR? |
| Users should select activity as dependent variable and all the other descriptors as independent variables. If users continue with the calculation from a previous run then they may choose the previous selection of dependent and independent variables. |
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| What could be a conventional ratio to select the test set for QSAR? |
| The test set for QSAR should be selected in ratio of 20-40%. Rest of the dataset should be selected as training set. |
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| What is the significance of the color code in QSAR worksheet? |
| Training data is shown in green rows and test data is shown in pink rows. Dependent variable data is shown in red font and independent variable data in black font. |
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| What is the significance of contribution chart? |
| Contribution chart displays contribution for variables in terms of percentage in the final equation of QSAR. |
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| What is the significance of correlation matrix? |
| Correlation matrix is useful to understand interdependence of columns while choosing descriptors for QSAR. |
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| How is a 3D QSAR model evaluated? |
Following are the guidelines for evaluating a new molecule design on electrostatic/ steric field ranges
- Electrostatic field
a) Negative range indicates that negative electrostatic potential is favorable for increase in the activity and hence a more electronegative substituent group is preferred in that region.
b) Positive range indicates that positive electrostatic potential is favorable for increase in the activity and hence a less electronegative substituent group is preferred in that region.
- Steric field
a) Negative range indicates that negative steric potential is favorable for increase in the activity and hence less bulky substituent group is preferred in that region.
b) Positive range indicates that positive steric potential is favorable for increase in the activity and hence more bulky substituent group is preferred in that region.
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| How to determine ranges of important field grid points in kNN-MFA? |
Steps to determine ranges of important field grid points in kNN-MFA
- Identify the important field grid points and their interaction type.
- Sort the worksheet on the basis of activity in ascending order.
- Choose k most active molecules i.e. k bottom most, to increase activity or k top most, to decrease activity of molecule.
- For the above chosen k most active molecules, collect the corresponding interaction energy values for the identified important field grid points.
- Find out minimum and maximum value of each field point on the basis of interaction energy values of k most active molecules to determine the corresponding range.
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| How can the models built by kNN-MFA QSAR be interpreted? |
| The green spheres show location where steric contribution has played important role and blue spheres are the locations where electrostatic contribution has played important role. Variation in bulk in these regions would help in improving the activity. The first value in the parenthesis indicates lower limit and the second value is the upper limit of steric/ electrostatic function values for molecules. The molecule adhering to these ranges at respective field locations are likely to be in the higher activity range. |
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| What is ProViz? |
| ProViz is a tool to study reaction mechanism and chemical processes at a molecular level. It helps in evaluation and visualization of three-dimensional molecular properties including those derived from ab initio quantum mechanical wave function obtained through programs like GAMESS and Gaussian. |
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| Does ProViz compute wavefunctions for molecules? |
| No. The wavefunction for a given molecule has to be obtained in terms of molecular orbitals from an external program. Once this is calculated, ProViz can read that output file (.out, .gam) and calculate various 3D molecular properties. |
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| How can various molecular properties be visualized using ProViz? |
ProViz provides high quality graphics tools for visualizing molecular scalar fields calculated over a grid in the form of
- Textured planes
- Contours in 2D and 3D
- Isosurfaces
- Textured vdW surface
ProViz also has the option to visualize the Molecular Orbitals (HOMO, LUMO). |
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| How is Grid utilized in ProViz? |
| All calculations of 3D properties are performed over a 3D Grid in ProViz. The default values of the grid are taken to be +4 Å or –4 Å from maximum/ minimum of the atomic coordinates of molecules on the screen. The default provided by MDS is a grid of 40 by 40 by 40 points. If the user wants to generate own grid, then there is provision for entering the Xmin, Xmax, Ymin, Ymax, Zmin, Zmax and number of points on each axis. |
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| What are the hydrophobicity calculation options? |
| Hydrophobicity distribution is calculated for a molecule over a 3D grid by extending its domain in each direction by 4 Å. Local hydrophobicity is evaluated at each and every grid point. XlogP and SlogP can be evaluated through ProViz. User can visualize the hydrophobicity distribution in the usual way in ProViz. |
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| What is ESP via point charges? |
| ProViz can calculate the charged based electrostatic potential (ESP via point charges) over a 3D grid. It uses the already available charges and in cases where the charges are unavailable it calculates the charges using Gasteiger Marsili method before calculating the potential. |
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What is pharmacophore? |
| Pharmacophore is a specific 3D map of biological properties including determining which are H bond donors, H bond acceptors, negative and positive charge centers, hydrophobes etc. that are common to all active set of ligands which exhibit a particular activity. |
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| How are the pharmacophoric features differentiated in MolSign? |
Different pharmacophoric features are represented by different colored spheres. The color code is as follows:
Buff color: Hydrogen bond acceptor.
Magenta color: Hydrogen bond donor.
Orange color: Aliphatic or aromatic carbon centre.
Green color: Negative charge centre.
Violet color: Positive charge centre.
Out of these spheres shown, the bigger spheres correspond to the actual pharmacophoric features that make up selected biophore. |
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| What are the steps for generating a pharmacophore? |
The steps for generating a pharmacophore are:
- Identify reference compound (for example: max activity)
- Generating properties of all molecules
- Finding out common 3D map of 3 to maximum common properties
- Alignment based on common properties
- Classic depiction of Biophores' pharmacophoric features with RMSD of alignment.
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| What are the Lipinski filters used in VLifeMDS? |
| Lipinski filters are based on hydrogen bond acceptor, hydrogen bond donor, number of rotatable bond, log P, molecular weight and polar surface area. These filters are based on original Lipinski's Rule of 5 and some extended parameters. LeadGrow gives scores to each molecule based on number of parameters satisfied. |
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| What is Lipinski Rule of 5? |
Lipinski's Rule of Five states that any drug like candidate should have:
- Not more than 5 hydrogen bond donors
- Not more than 10 hydrogen bond acceptors
- A molecular weight under 500 g/mol
- A partition coefficient log P less than 5
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| How can I validate the model that I have generated? |
| Users can validate the generated model using functionality detect criss-cross residues, local geometry check and Ramchandran plot. |
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| What are the different scoring functions for docking in Biopredicta? |
| The different scoring functions utilized are Dock Score, steric, steric + electrostatic & PLP Score |
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| Can I use my own scoring functions? |
| No |
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| Can I do docking with the flexibility of the ligand? |
| Yes. BioPredicta provides options for complete flexible docking keeping both the receptor and ligand flexible. |
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| How can I identify the active site to dock the ligand into given protein? |
| Users can use the functionality identify cavity from menu for a given protein. From the number of cavities identified one can choose appropriate cavity as an active site based on the residues involved in that cavity. |
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| What is VLifeSCOPE? |
| VLifeSCOPE is a receptor-dependent QSAR method that provides better understanding of ligand-receptor interactions. |
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| Is VLifeSCOPE modeling different from QSAR modeling? |
| VLifeSCOPE involves breaking down and analyzing the docking interactions into individual active site residue contributions. These contributions then become descriptors for QSAR modeling. The regression model to be chosen for QSAR depends on user. |
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| Can I dock ligand into DNA using VLifeMDS? |
| Not yet. |
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| I want to see two proteins together for comparison, what shall I do? |
| The BioPredicta Superimpose functionality can enable visualization of two proteins simultaneously. |
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| What is PLP docking? |
| The Piecewise Linear Pairwise Potential (PLP) scoring function in rigid docking method includes ligand-receptor interactions of hydrogen bonding (donor-acceptor), repulsions (donor-donor, acceptor-acceptor) and dispersion (involving non-polar group interactions) types. This is essentially a rigid batch docking method where unique conformers of a set of ligands can be fed in as input. This docking method gives option for ligand guided or cavity guided docking. If the co-crystallized ligand structure is available, user can choose this as reference ligand. In case there is no co-crystallized ligand, the grids will be constructed around the reference cavity, which is the active site cavity as specified by user. Each of the ligands to be docked will then be placed at these grid points and these interaction energy terms will be evaluated. The total energy, which consists of all these energy terms, will be minimized to get a corresponding PLP score. Out of all possibilities, thirty top ligand poses together with their PLP score energy and the minimum score as the best pose are reported for each ligand. |
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| What are the molecule file formats that I can use to create my database? |
| Users can create database, using *.mds, *.mol2, *.sdf, *.smi molecule file formats. |
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| Can I create database using files having different (molecule file) formats at the same time? |
| Yes. All supported files for input should be located in single folder. |
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| Can I tag database with supplementary notes? |
| Yes. One can add supplementary notes while creating database as additional comments. Users can view or add additional comments with database manager. |
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| What is the difference between user and standard database? |
| Standard databases are the databases provided with ChemXplor whereas the databases created or imported by user will be considered as user database. Only user databases are allowed to be deleted. |
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| How can I retrieve structure of molecules found in search result? |
| Users can retrieve structure of molecules found in search result using File > Save Result as Molecule menu option. This selected result molecules will be stored in the specified folder. Usesr also have facility to select different file format while saving molecules. |
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| How can I view descriptor values of molecules found in search result? |
| Search result shows descriptor information of only those descriptors, which are used while searching. Apart from search result displayed user can view PhysicoChemical descriptors and Atom type counts. |
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| Can I use result of database search for another search? |
| Users can save search result as database and this database can be used for second search. |
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| Can I use search result information in other application? |
| Currently ChemXplor supports information export in *.csv & *.xls format. |
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| Since ChemXplor can display multiple search result at a time, how can I identify result based on query used for results? |
| The query dialogs query type sections have information of query used for selected search results. |
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