What if I have a question that is not answered here or in the manual? Installation Questions. How is dms installed? Should AMBERHOME be. This tutorial introduces DOCK Score in DOCK6 and describes the preparation of input Please see the DOCK6 manual for futher details. If you have installed DOCK6, this script can be found in the bin directory. . To select other options, please read the DOCK 6 Manual.
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Torsion Pre-minimizer By default, the simplex minimizer in DOCK treats the six rigid degrees of freedom 3 translational, 3 rotational and each torsion equally. Preferably, the molecule should be prepared with hydrogens and charges using AMBER and subsequently converted to mol2 format using the ‘top2mol2’ command. For example, you can rename the old. Ligand pose comparisons using standard red dck6, max 3 anchors blueor max 1 anchor green protocols.
A particularly useful way to evaluate cross-docking performance is to employ heatmapsas illustrated for a representative family in Figure 3. Yuriev E, Ramsland PA. In practice, however, enrichment results are highly system-dependent and subject not only to the specific computational protocols employed, but also the experimental assays used to evaluate activity.
Ligand order along the y-axis is determined lexicographically first by success rate number of blue squaresthen by scoring failures number of green squaresthen by sampling failures number of red squaresand finally by the number of non-viable pairings number of gray squares.
We can open the output box file in chimera to make sure the box is in the right place. Find the job id for the one you want to delete, and do:. Receptors were protonated and assigned ff99SB parameters [ 54 ] in tLEaP AmberToolsthen subjected to short energy minimizations with heavy restraints on non-hydrogen atoms using sander Amber Turning our attention to HIV protease, we observed a low matrix success rate Because there is only one degree of freedom in the torsion pre-minimization stage, a small number of iterations still provides the desired result.
As part of the SB release, 24 cross-docking families were prepared ranging from 6 to 59 systems per family and made available for download.
DOCK 6: Impact of New Features and Current Docking Performance
Note that the repulsive-only component of the van der Waals term is always unfavorable, so it will serve only to prevent internal clashes between ligand heavy atoms, which is the primary goal of the function. This tutorial is based on the shell tcshand maybe you are using a different shell. So what you will do is, first you open the receptor file 1DF8.
The observed specificity of indomethacin for COX-2 and of ibuprofen analogs for COX-1 is consistent with the experimental specificity for inhibitors of the two cyclooxygenase isoforms.
Use the following format:. Taken together, these observations could suggest that mutations that confer drug resistance in HIV reverse transcriptase might be more easily identified from non-viable pairings than from cross-docking outcomes, although additional studies need to be performed.
If there is no anchor bigger than five atoms, then the biggest with the most branching points is chosen.
The steady progression of features and performance from version 4 to 5 to 6 is a testament to the importance of employing multiple metrics and large data sets for validation, to the advantages of an open source infrastructure, and to the benefits of a large community of users and developers, past and present.
Figure 16 shows the top five pose overlays from each of the five enrichment studies.
2012 DOCK tutorial with Streptavidin
Pose Reproduction Methods The first key experiment, pose reproduction, involves taking a known i. Chemical Computing Group; Kuntze and Robert C. If the grid is created in the incorrect location, the ligand binding sites will be sampled within the grid, and the best binding site will not be sampled. To resolve this problem, we implemented a torsion pre-minimizer that disregards all degrees of freedom except the dihedral angle of the newly added fragment.
See other articles in PMC that cite mmanual published article. Structures are grouped by the identity of the bound ligand: Table 2 Comparison of different numbers of anchors to assess pose reproduction in SB Interestingly however, the RMSD restraint minimizer and the torsion pre-minimizer both negatively impact success when using the FLX docking protocol.
Where C 1 …C N are user-input coefficients, and F 1 …F N are user-chosen scoring functions such as the rock6 energy score, footprint similarity score, pharmacophore matching score, volume matching score, and chemical fingerprint, among others.
Unable to save thumbnail to destination. Parallel computing can reduce the running time of virtual screening. Save the surface as 1DF8. Simplex minimization energy evaluation then attempts to minimize the sum:. As expected, RMSD differences for max 3 anchors vs. Typically the reference molecule will be an endogenous substrate or kanual inhibitor from an x-ray crystallographic structure.
This dramatically improves docking proficiency compared to using no internal energy functionas well as overall sampling. Of the eight streptavidin ligands Figure 12bfive are biotin or a biotin derivative [ 83 — 86 ] and three are azobenzene analogs.
To generate docking spheres, we need to use a command line program called sphgen. New input parameters have provided users more control over the number and identity of anchors that are used for docking Figure 6Table 2which may mmanual to faster, more efficient docking under the present anchor-and-grow strategy.