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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Cross-docking outcomes for 24 families. Another likely reason for the high incidence of scoring vock6 among this group is failure to account for water-mediated interactions or solvation effects, which are important to both carbonic anhydrase [ 9798 ] and lysozyme. To correct this behavior we modified the internal energy function to employ solely the repulsive van der Waals term, and to function at all stages of growth.

DOCK 6: Impact of New Features and Current Docking Performance

To measure the effect of receptor mutations in DOCK, we consider the drug darunavir with both wild type dokc6 mutant protease. As one representative example from a large sampling ensemble, Figure 7 shows that, when the RMSD restraint minimizer is used, ligand growth proceeds in a highly methodical fashion and without sudden changes in RMSD. These enhancements are described in further detail in the Supporting Information.

In addition, the new top2mol2 tool allows for facile conversion between Amber parm and crd files and separate receptor, ligand, and cofactor mol2 files Tripos Sybyl conventions [ 55 ] while retaining the atomic partial charges, bond types, and atom types as assigned by tLEaP receptor or antechamber ligand, cofactors.

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. A msnual clash overlap parameter near 1 can negatively impact sampling, while a low parameter near 0 docck6 allow too many unphysical ligand conformers to appear.


Note that these are just a few representative examples of the known limitations to docking, and factors such as entropic effects, induced fit effects, and others also present challenges to successful docking. The standard FLX, LAS, and FAD protocols described above are accompanied here by the rigid docking protocol RGDwherein ligands are docked to the receptor rigidly constrained in the starting crystallographic conformation and without sampling any dihedral torsions.

Open sph file, delete that sphere and modify the number of spheres in that cluster. Increase the number of these parameters can lead to increased running time. Since the computational cost of virtual screening is much higher than single-ligand docking, it is better for us to run it doc6 Seawulf.

Gasteiger J, Marsili M. The remainder of the mqnual focuses on DOCK version 6. If the manua is greater than the distance between the pair of atoms, a clash is registered and the conformer is rejected from the ensemble.

This will allow you to have only the ligand. Across a large test set, e.

DOCK 6: Impact of New Features and Current Docking Performance

Importantly, the new protocols enable the energy minimization of newly-added receptor hydrogen atoms in the presence of the bound cognate ligand and cofactor, if applicableallowing for physically reasonable positioning.

As described in Mukherjee et al[ 47 ] DOCK success rates are typically higher when the exact anchor position is known, as is the case for fixed anchor docking FAD and the majual atom spheres protocol LAS discussed in Minimization Options below. Cross-docking Xock6 The second key experiment, cross-docking, provides an additional metric for evaluating docking performance over a very large set of protein-ligand pairs.

Counterintuitively, we observed an increase in docking success Low sampling failure rate and few non-viable pairings indicate that the manyal as a group are amenable to accommodating all ligands in the group. Typically, X-ray crystal structures from the PDB do not contain hydrogen atoms, and as a result, they must be added eock6 the model prior to docking.


Both of these observations are consistent with the experimental specificity of lapatinib for inactive forms of EGFR and the other ligand classes for active forms of EGFR.

Cells in the matrix are color-coded using the docking outcome definitions previously described for pose reproduction experiments: University of California; Use this link Wiki Markup as a reference for editing the wiki. Hydrogens and protein atoms hidden for clarity. Thus, in LAS, the anchor will have a high propensity for finding the correct anchor position, but will also find several decoy positions, making the problem slightly more challenging than FAD. Accounting for explicit water molecules as a component of the receptor, for example, can help improve accurate pose reproduction predictions.

Within dok6 family, the receptors adopt local variations in conformation due in part to the identity of the co-crystallized ligands see Figure 10 ; also discussed in Manial Information, Figure S1which fall into several classes: Further questions will be asked during the run.

This tutorial was developed collaboratively by the AMS class of A consequence of better dovk6 and scoring using internal energy is an increase in average docking time from 2.

The effectiveness of DOCK is demonstrated in pose reproduction, cross-docking picturedand enrichment experiments to systems that are of interest as drug targets. New input parameters have provided users more control over the number and identity of anchors that are used for docking Figure 6Table 2which may lead to faster, more efficient docking under the present anchor-and-grow strategy.

Similar calculations can be made to determine the matrix scoring failure rate green squaresthe matrix sampling failure rate red squaresor the success and failure rates pertaining to the diagonal.