AutoDock Vina significantly improves the average accuracy of the binding mode predictions compared to AutoDock 4, judging by our tests on the training set used in AutoDock 4 development.[*]
Additionally and independently, AutoDock Vina has been tested against a virtual screening benchmark called the Directory of Useful Decoys by the Watowich group, and was found to be "a strong competitor against the other programs, and at the top of the pack in many cases". It should be noted that all six of the other docking programs, to which it was compared, are distributed commercially.
AutoDock Tools Compatibility
For its input and output, Vina uses the same PDBQT molecular structure file format used by AutoDock. PDBQT files can be generated (interactively or in batch mode) and viewed using MGLTools. Other files, such as the AutoDock and AutoGrid parameter files (GPF, DPF) and grid map files are not needed.
Binding mode prediction accuracy on the test set. "AutoDock" refers to AutoDock 4, and "Vina" to AutoDock Vina 1.
Ease of Use
Vina's design philosophy is not to require the user to understand its implementation details, tweak obscure search parameters, cluster results or know advanced algebra (quaternions). All that is required is the structures of the molecules being docked and the specification of the search space including the binding site. Calculating grid maps and assigning atom charges is not needed. The usage summary can be printed with "
vina --help". The summary automatically remains in sync with the possible usage scenarios.
Flexible Side Chains
Like in AutoDock 4, some receptor side chains can be chosen to be treated as flexible during docking.
AutoDock Vina tends to be faster than AutoDock 4 by orders of magnitude.[*]
Additionally, Vina can take advantage of multiple CPUs or CPU cores on your system to significantly shorten its running time.
World Community Grid
Qualified projects can run AutoDock Vina calculations for free on the massively parallel World Community Grid. Existing projects using AutoDock Vina there include those targeting Malaria, Leishmaniasis and Schistosomiasis. Some of these projects average over 50 years worth of computation per day.
Average time per receptor-ligand pair on the test set. "AutoDock" refers to AutoDock 4, and "Vina" to AutoDock Vina 1.
What is the meaning or significance of the name "Vina"? Why was it developed?
Please see this mailing list post.
How accurate is AutoDock Vina?
It should be noted that the predictive accuracy varies a lot depending on the target, so it makes sense to evaluate AutoDock Vina against your particular target first, if you have known actives, or a bound native ligand structure, before ordering compounds. While evaluating any docking engine in a retrospective virtual screen, it might make sense to select decoys of similar size, and perhaps other physical characteristics, to your known actives.
What is the difference between AutoDock Vina and AutoDock 4?
AutoDock 4 (and previous versions) and AutoDock Vina were both developed in the Molecular Graphics Lab at The Scripps Research Institute. AutoDock Vina inherits some of the ideas and approaches of AutoDock 4, such as treating docking as a stochastic global opimization of the scoring function, precalculating grid maps (Vina does that internally), and some other implementation tricks, such as precalculating the interaction between every atom type pair at every distance. It also uses the same type of structure format (PDBQT) for maximum compatibility with auxiliary software.
However, the source code, the scoring funcion and the actual algorithms used are brand new, so it's more correct to think of AutoDock Vina as a new "generation" rather than "version" of AutoDock. The performance was compared in the original publication [*], and on average, AutoDock Vina did considerably better, both in speed and accuracy. However, for any given target, either program may provide a better result, even though AutoDock Vina is more likely to do so. This is due to the fact that the scoring functions are different, and both are inexact.
What is the difference between AutoDock Vina and AutoDock Tools?
AutoDock Tools is a module within the MGL Tools software package specifically for generating input (PDBQT files) for AutoDock or Vina. It can also be used for viewing the results.
Can I dock two proteins with AutoDock Vina?
You might be able to do that, but AutoDock Vina is designed only for receptor-ligand docking. There are better programs for protein-protein docking.
Will Vina run on my 64-bit machine?
Yes. By design, modern 64-bit machines can run 32-bit binaries natively.
Why do I get "can not open conf.txt" error? The file exists!
Oftentimes, file browsers hide the file extension, so while you think you have a file "
conf.txt", it's actually called "
This setting can be changed in the control panel or system preferences.
You should also make sure that the file path you are providing is correct with respect to the directory (folder) you are in,
e.g. if you are referring simply to
conf.txt in the command line, make sure you are in the same directory (folder)
as this file. You can use
dir commands on Linux/MacOS and Windows, respectively, to list the contents
of your directory.
Why do I get "usage errors" when I try to follow the video tutorial?
The command line options changed somewhat since the tutorial has been recorded. In particular, "
--out" replaced "
Vina runs well on my machine, but when I run it on my exotic Linux cluster, I get a "boost thread resource" error. Why?
Your Linux cluster is [inadvertantly] configured in such a way as to disallow spawning threads. Therefore, Vina can not run. Contact your system administrator.
Why is my docked conformation different from what you get in the video tutorial?
The docking algorithm is non-deterministic. Even though with this receptor-ligand pair, the minimum of the scoring function corresponds to the correct conformation, the docking algorithm sometimes fails to find it. Try several times and see for yourself. Note that the probability of failing to find the mininum may be different with a different system.
My docked conformation is the same, but my energies are different from what you get in the video tutorial. Why?
The scoring function has changed since the tutorial was recorded, but only in the part that is independent of the conformation: the ligand-specific penalty for flexibility has changed.
Why do my results look weird in PyMOL?
PDBQT is not a standard molecular structure format. The version of PyMOL used in the tutorial (0.99rc6) happens to display it well (because PDBQT is somewhat similar to PDB). This might not be the case for newer versions of PyMOL.
Any other way to view the results?
You can also view PDBQT files in PMV (part of MGL Tools), or convert them into a different file format (e.g. using AutoDock Tools, or with "save as" in PMV)
How big should the search space be?
As small as possible, but not smaller. The smaller the search space, the easier it is for the docking algorithm to explore it.
On the other hand, it will not explore ligand and flexible side chain atom positions outside the search space. You should probably avoid search spaces bigger than
30 x 30 x 30 Angstrom, unless you also increase "
Why am I seeing a warning about the search space volume being over 27000 Angstrom^3?
This is probably because you intended to specify the search space sizes in "grid points" (0.375 Angstrom), as in AutoDock 4.
The AutoDock Vina search space sizes are given in Angstroms instead. If you really intended to use an unusually
large search space, you can ignore this warning, but note that the search algorithm's job may be harder.
You may need to increase the value of the
exhaustiveness to make up for it. This will lead to longer run time.
The bound conformation looks reasonable, except for the hydrogens. Why?
AutoDock Vina actually uses a united-atom scoring function, i.e. one that involves only the heavy atoms. Therefore, the positions of the hydrogens in the output are arbitrary. The hydrogens in the input file are used to decide which atoms can be hydrogen bond donors or acceptors though, so the correct protonation of the input structures is still important.
What does "exhaustiveness" really control, under the hood?
In the current implementation, the docking calculation consists of a number of independent runs, starting from random conformations.
Each of these runs consists of a number of sequential steps. Each step involves a random perturbation of the conformation followed
by a local optimization (using the Broyden-Fletcher-Goldfarb-Shanno algorithm) and a selection in which the step is either accepted or not.
Each local optimization involves many evaluations of the scoring function as well as
its derivatives in the position-orientation-torsions coordinates.
The number of evaluations in a local optimization is guided by convergence and other criteria.
The number of steps in a run is determined heuristically, depending on the size and flexibility of the ligand and the flexible side chains.
However, the number of runs is set by the
Since the individual runs are executed in parallel, where appropriate,
exhaustiveness also limits the parallelism.
Unlike in AutoDock 4, in AutoDock Vina, each run can produce several results:
promising intermediate results are remembered.
These are merged, refined, clustered and sorted automatically to produce the final result.
Why do I not get the correct bound conformation?
It can be any of a number of things:
Why don't I get as many binding modes as I specify with "
This option specifies the maximum number of binding modes to output.
The docking algorithm may find fewer "interesting" binding modes internally.
The number of binding modes in the output is also limited by the "
which you may want to increase.
Why don't the results change when I change the partial charges?
AutoDock Vina ignores the user-supplied partial charges. It has its own way of dealing with the electrostatic interactions through the hydrophobic and the hydrogen bonding terms. See the original publication [*] for details of the scoring function.
I changed something, and now the docking results are different. Why?
Firstly, had you not changed anything, some results could have been different anyway, due to the non-deterministic nature of the search algorithm.
Exact reproducibility can be assured by supplying the same random
seed to both calculations, but only if all other inputs and
parameters are the same as well. Even minor changes to the input can have an effect similar to a new random seed.
What does make sense discussing are
the statistical properties of the calculations:
e.g. "with the new protonation state, Vina is much less likely to find the correct docked conformation".
How do I use flexible side chains?
You split the receptor into two parts: rigid and flexible, with the latter represented somewhat similarly to how the ligand is represented.
See the section "Flexible Receptor PDBQT Files" of the
AutoDock4.2 User Guide (page 14) for how to do this
in AutoDock Tools.
Then, you can issue this command:
vina --config conf --receptor rigid.pdbqt --flex side_chains.pdbqt --ligand ligand.pdbqt.
Also see this write-up on this subject.
How do I do virtual screening?
Please see the relevant section of the manual.
Please note that a variety of docking management applications exist to assist you in this task.
I don't have sufficient computing resources to run a virtual screen. What are my options?
You may be able to run your project on the World Community Grid, or use Docking@UTMB. See Other Software.
Will you answer my questions about Vina if I email or call you?
No. Vina is community-supported. There is no obligation on the authors to help others with their projects. Please see this page for how to get help.
If you are using Cygwin, the above command would instead be"\Program Files\The Scripps Research Institute\Vina\vina.exe" --help
See the Video Tutorial for details. Don't forget to check out Other Software for GUIs, etc./cygdrive/c/Program\ Files/The\ Scripps\ Research\ Institute/Vina/vina --help
Optionally, you can copy the binary files where you want.tar xzvf autodock_vina_1_1_2_linux_x86.tgz
If the executable is in your./autodock_vina_1_1_2_linux_x86/bin/vina --help
PATH, you can just type "
vina --help" instead. See the Video Tutorial for details. Don't forget to check out Other Software for GUIs, etc.
Optionally, you can copy the binary files where you want.tar xzvf autodock_vina_1_1_2_mac.tgz
If the executable is in your./autodock_vina_1_1_2_mac/bin/vina --help
PATH, you can just type "
vina --help" instead. See the Video Tutorial for details. Don't forget to check out Other Software for GUIs, etc.
split, with the source code from the appropriate subdirectories.
libmust be a library, that the other projects depend on, and
splitmust be console applications. For optimal performance, remember to compile using the
On OS X and Linux, you may want to navigate to the appropriate
build subdirectory, customize the
by setting the paths and the Boost version, and then type
make depend make
Input: --receptor arg rigid part of the receptor (PDBQT) --flex arg flexible side chains, if any (PDBQT) --ligand arg ligand (PDBQT) Search space (required): --center_x arg X coordinate of the center --center_y arg Y coordinate of the center --center_z arg Z coordinate of the center --size_x arg size in the X dimension (Angstroms) --size_y arg size in the Y dimension (Angstroms) --size_z arg size in the Z dimension (Angstroms) Output (optional): --out arg output models (PDBQT), the default is chosen based on the ligand file name --log arg optionally, write log file Misc (optional): --cpu arg the number of CPUs to use (the default is to try to detect the number of CPUs or, failing that, use 1) --seed arg explicit random seed --exhaustiveness arg (=8) exhaustiveness of the global search (roughly proportional to time): 1+ --num_modes arg (=9) maximum number of binding modes to generate --energy_range arg (=3) maximum energy difference between the best binding mode and the worst one displayed (kcal/mol) Configuration file (optional): --config arg the above options can be put here Information (optional): --help display usage summary --help_advanced display usage summary with advanced options --version display program version
In case of a conflict, the command line option takes precedence over the configuration file one.receptor = hsg1/rigid.pdbqt ligand = ligand.pdbqt center_x = 2 center_y = 6 center_z = -7 size_x = 25 size_y = 25 size_z = 25 energy_range = 4
exhaustiveness, the time spent on the search is already varied heuristically depending on the number of atoms, flexibility, etc. Normally, it does not make sense to spend extra time searching to reduce the probability of not finding the global minimum of the scoring function beyond what is significantly lower than the probability that the minimum is far from the native conformation. However, if you feel that the automatic trade-off made between exhaustiveness and time is inadequate, you can increase the
exhaustivenesslevel. This should increase the time linearly and decrease the probability of not finding the minimum exponentially.
rmsd/lb(RMSD lower bound) and
rmsd/ub(RMSD upper bound), differing in how the atoms are matched in the distance calculation:
rmsd/ubmatches each atom in one conformation with itself in the other conformation, ignoring any symmetry
rmsd'matches each atom in one conformation with the closest atom of the same element type in the other conformation (
rmsd'can not be used directly, because it is not symmetric)
rmsd/lbis defined as follows:
rmsd/lb(c1, c2) = max(rmsd'(c1, c2), rmsd'(c2, c1))
The advanced options allow
--score_only"; see the paper for what the terms are)
The examples below assume that Bash is your shell. They will need to be adapted to your specific needs.
To perform virtual screening on Windows, you can either use Cygwin and the Bash scripts below, or, alternatively, adapt them for the Windows scripting language.
Suppose you are in a directory containing your receptor
a set of ligands named
You can create a configuration file
conf.txt, such as
and dock all ligands with this shell script. The script assumes thatreceptor = receptor.pdbqt center_x = 2 center_y = 6 center_z = -7 size_x = 25 size_y = 25 size_z = 25 num_modes = 9
vinais in your
PATH. Otherwise, modify it accordingly.
If you have a Linux Beowulf cluster, you can perform the individual dockings in parallel.
Continuing with our example, instead of executing
all the dockings in a loop locally,
we will write one
*.job script per ligand,
(a PBS command)
to schedule these scripts to be executed by the cluster.
Run this shell script to do it.
The script assumes that
qsub are in your
Otherwise, modify it accordingly.
Once the jobs have been scheduled, you can monitor their status with
qstat -u `whoami`
Selecting Best Results
If you are on Unix and in a directory that contains directories with PDBQT files, all of which are AutoDock Vina results, you may find this Python script useful for selecting the top results. Run it as:
to get the file names of the top 10 hits, which can then be easily copied.vina_screen_get_top.py 10
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 31 (2010) 455-461
ls conf.txtto see if the file is really there)