Autodock Vina

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We thank Mgr. Jiří Wiesner for writting following text.

Description

AutoDock Vina is a new program for drug discovery, molecular docking and virtual screening, offering partial receptor flexibility, multi-core capability, high performance and enhanced accuracy and ease of use. AutoDock Vina achieves an approximately two orders of magnitude speed-up compared with the molecular docking software AutoDock 4, while also significantly improving the accuracy of the binding mode predictions. On a typical modern workstation, Vina should often be able to reliably generate the predicted binding modes and affinities of a ligand in seconds to minutes, depending on the ligand complexity.

Reference

O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry (in press)

Availability

Program is actually available in version 1.0.2 and 1.1.2

Use

The current versions available in Meta centrum are vina-1.0.2 and vina-1.1.2. The executable is 32-bit, but runs on 64-bit systems with 32-bit compatibility libraries.

Documentation

Licence

User have to agree with licence

Supported platforms

Linux

Program administrator

meta@cesnet.cz

Homepage

http://vina.scripps.edu/

Detailed documentation

IMPORTANT!!

0. Do I always have to specify the number of CPUs being used by Vina?

Yes, unless you are using the whole node for that particular job. Vina, if not restricted, automatically claims to use all processors on the node.

Preparation

1. What input format does Vina use for receptor and ligand files?

The input format is PDBQT format, which is also used by Autodock4. PDBQT format is an extended pdb format with atomic charge and atom type information located in separate columns behind the coordinate columns.

2. What is the preferred application for preparation of PDBQT files?

AutoDockTools which is a part of MGLTools, web page: http://mgltools.scripps.edu. Search for the detailed instructions on the pdbqt conversion on this web page: http://autodock.scripps.edu/faqs-help/tutorial/using-autodock-4-with-autodocktools. The instructions on preparation of flexible receptor sidechains are also included.

3. What kind of charges should the PDBQT files contain? Gasteiger, RESP on HF/6-31G* level?

The charges may be zero in fact, Vina does not use any charges at all.

4. How do I define the search space? Vina uses a grid, does it?

Yes, Vina uses a grid which is defined by its center and number of points in each dimension. The grid spacing is always set to 1A and its purpose is just to inform Vina about the size of the search space; it has nothing to do with the accuracy of the computation. AutoDockTools is the preferred application to visualize the grid - search space, see the above mentioned tutorial.

Usage

1. How do I run a calculation?

The calculation can be set up by using command line arguments or a configuration file. To display the available command line arguments type "vina --help". The configuration file syntax is: "command_line_argument = value", each argument on its separate line. To run a calculation with a config file type "vina --config CONFIG_FILE_NAME". Configuration file, example: receptor = ../../1xlw_spo_rigid.pdbqt flex = ../../1xlw_spo_flex.pdbqt ligand = ../../K05.pdbqt

center_x = -2.518 center_y = 4.689 center_z = -9.073 size_x = 28 size_y = 32 size_z = 28

out = K05_out.pdbqt

cpu = 1 exhaustiveness = 8

2. What does the exhaustiveness parameter mean?

It influences the thoroughness of the global search algorithm. Larger values increase the probability of finding the global minimum, but also extend the computational time. Increasing the exhaustiveness value increases the time linearly and decreases the probability of not finding the minimum exponentially. Apart from exhaustiveness influenced by users, Vina has an internal heuristic algorithm to extend the search in accordance with an increasing number of atoms and rotatable bonds.

3. How long does a typical Vina docking run take?

Exhaustiveness 8, 20 rotatable torsions, need about 14 minutes on one processor.

4. But... There is something wrong! AFAIK, AutoDock4 used grid too, but the grid has to be calculated in advance, it also uses grid configuration file and docking configuration file... and things are much more complicated. How come?

Vina uses grid to compute energies, but it automatically calculates the grid maps, no other configuration files, except the one described above and even that is optional, are need. Yes is really so simple! Vina also clusters the results for you, hence no endeavors in this direction are requested from you either.

Visualization

1. How do display the docking results? Use Pymol. PDBQT files can be directly opened, you have to display them by displaying all files. Use arrows to switch between different ligand binding modes.

2. I see incorrectly oriented hydrogens in the ligand and flexible receptor parts. How is this possible?

Vina uses a united-atom scoring function. In Vina, the degrees of freedom that only move hydrogens, such as the hydroxyl group torsions, are degenerate. Therefore, in the output, some hydrogen atoms can be expected to be positioned randomly (but consistent with the covalent structure). For a united-atom treatment, this is essentially a cosmetic issue.