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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DOCK 6: Impact of New Features and Current Docking Performance
A substantial speed-up of the new internal energy code was accomplished by building a pair-list of atoms that could form a van der Waals interaction internal to the ligand. Visual inspection of docking outcomes to carbonic anhydrase reveals that the zinc ion in the active site frequently coordinates the incorrect atom from the sulfonamide group [ 91 ] present in all 29 ligands from this familyor coordinates atoms in the sulfonyl group [ 92 ] present in 14 ligands from this familyall of which are highly polarized.
Progress toward improved scoring, however, is observed with each new release of DOCK, as scoring failure rates follow the series Biotin is a water soluble B-vitamin complex which is composed of an ureido tetrahydroimidizalone ring fused with a tetrahydrothiophene ring.
You can again visualize it by showsphere. Despite this somewhat surprising negative result with respect to the FLX docking protocol, examination of the growth steps for docking with and without the RMSD restraint shows that the algorithm produces the expected behavior.
These ,anual plot the true positive rate true positives divided by the total number of positives, also called sensitivity against the false positive rate false positives divided by the total number of decoys, also described as [1-specificity] for a rank-ordered list. You can apply this same strategy to then sync files with your home computer as well. Cross-docking outcomes for 24 families. To generate docking spheres, we need to use a command line program called sphgen.
RMSD Restraint Minimizer Our initial testing demonstrated that the torsion pre-minimization cannot always satisfactorily resolve clashes between a ligand and receptor. Obviously, the reference molecule is not correct in this case.
The translational, rotational, and torsional step sizes for the simplex minimizer were 1. And, although the sampling failure rate for DOCK 6. In this case, different van der Waals coefficients appeared to affect the actives more so than the decoys, ultimately leading to worse overall enrichment. On-the-fly docking protocols that includes both receptor and ligand flexibility in DOCK are under investigation.
Increase the number of these parameters can lead to increased running time. To discuss some specific cross-docking outcomes in detail while maintaining brevity, the results below are arranged into four main categories: During energy minimization, this unfavorable score is added to the intermolecular interaction energy computed, for example, fock6 the gridand the sum of the two energies is minimized.
Then, a small number manial iterations of energy minimization are performed typically 10 to 50prior to a full energy minimization with the standard degrees of freedom. This observation follows our expectations, and it demonstrates that DOCK performs optimally when searching for cognate receptor-ligand binding poses.
In the case of carbonic anhydrase and lysozyme, the docking outcomes are dominated by scoring failures Briefly, for every non-bonded pair of ligand atoms, the clash overlap function sums the two van der Waals radii and multiplies that value by a user-specified clash overlap parameter ranging from 0 to 1. Summary and Future Perspectives As the seminal docking program in continual development since the early dockk6, DOCK has evolved through major algorithmic additions, updates, and rewrites, and with considerable community input due to its widespread use.
As expected, scrambling the results by randomly choosing actives and decoys generates curves that lie on the ROC diagonals black lines. Ongoing work in our group and by others [ 38 dock, — ] is seeking to address this challenge. Forli S, Olson AJ. However, if all ligand degrees of freedom are treated equally, the minimizer may prefer the entire ligand pose to be rigidly translated or rotated away from the source of the clash, rather than adjusting the torsion.
In this specific example, five actives represented by black circles and ten decoys represented by open circles are shown.
To generate the grid we will use the grid program. Although a complete example input file is distributed with the test set, manhal of the important parameters are as follows: Supplementary Material Supp Material Click here to view. And then use the ViewDock function of Chimera to look at your 47 ligands one or however many you want at a time.
Of the eight streptavidin ligands Figure 12bfive are biotin or a biotin derivative [ 83 — 86 ] and three are azobenzene analogs. Here, ligands are labeled along the y -axis, and receptors are labeled in the same order along the x -axis.
The average diagonal success rate is As an example, active and inactive conformations of EGFR were retained in the same family. However, it is possible that a newly grown torsion coarsely sampled at the angles specified in the DOCK mznual definition file [ 56 ] could introduce clashes with the receptor.
DOCK 6: Impact of New Features and Current Docking Performance
These results may be useful as a reference to the reader to identify specific PDB structures that are amenable to docking or virtual screening experiments, or to quickly assess how DOCK 6. Figure 11 shows cross-docking outcomes using the standard FLX protocol with the SGE scoring function plotted onto 24 separate heatmaps, sorted left-to-right, top-to-bottom by decreasing docking success rate.
The new RMSD metric contributes to maunal accurate reporting of DOCK successes and failures Figure S2and it manuaal also been co-opted to serve as a scoring function or applied to molecular dynamics doco6. It is also involved in gluconeogenesis. So you need either copy your ligand file to manul current directory or specify the correct path of your ligand file like below:. In the case of matrix metalloproteinase, the scoring and sampling failures are roughly equal This increase, however, is not due to the time required for internal energy calculations mankal, rather it is primarily due to the larger number of anchor-and-grow conformer branches see Figure 1 retained.
Accounting janual explicit water molecules as a mxnual of the receptor, for example, can help improve accurate pose reproduction predictions.
The purpose of virtual screening is different from single molecule docking, so we need to modify our previous docking script dock.
The remainder of the manuscript focuses on DOCK version 6. However, some aligned ligand poses may not fit in a non-native binding site due to, for example, induced fit effects or receptor mutations, and thus should not be used as a docking reference. In addition, most of the important files that are derived from the original crystal structure will be given a prefix that is the same as the PDB code, ‘1DF8’.
Other new features, including a footprint similarity scoring function, a symmetry-corrected RMSD algorithm, a database filter, and docking forensic tools are briefly summarized, then described in more detail in Supporting Information. The other five ligands are ibuprofen and ibuprofen analogs, [ ] and for the 4COX receptor, only one of these successfully docked.
Ligand-atom spheres LAS is the same as FLX, with the exception that only the positions of heavy atoms from the crystallographic ligand are used as spheres and, subsequently, for orienting the anchors. Specify the following path:.