[Dock-fans] amber score regarding cofactor FAD
gongxingwen at 163.com
Tue May 4 22:41:26 PDT 2010
I am conducting a virtual screening targeting an enzyme containing a cofactor FAD. However, the cofactor FAD cannot be recognized by DOCK6.3 when preparing for amber score. I have resolved this problem using AMBER9 suite. I found a AMBER parameter database at http://www.pharmacy.manchester.ac.uk/bryce/amber#cof. Could these parameters be included in next version of DOCK ? It would be very helpful for docking.
Xing-Wen Gong (Ph.D)
> 发件人: "Scott Brozell" <sbrozell at rci.rutgers.edu>
> 发送时间: 2010年5月5日 星期三
> 收件人: dock-fans at docking.org
> 主题: [Dock-fans] Announcing: Release of DOCK 6.4
> Dear DOCK Users,
> We are proud to announce the official release of DOCK version 6.4,
> which includes several new features (see below for details).
> Documentation and tutorials for this release can be found at
> If you already have an academic DOCK 6 license and you still have
> download slots available, then you can use your original download
> information to acquire DOCK 6.4. If you have used all your download
> slots then request a refresh in an email to
> dock_license at dock.compbio.ucsf.edu.
> If you have never applied for an academic DOCK 6 license then apply at
> Thank you for your continued interest in DOCK. We hope this software is
> a useful part of your design efforts.
> The DOCK Team
> Please visit us at the DOCK Web site.
> --- * ---
> DOCK 6.4
> For version 6.4, recent improvements to the sampling implementation and
> corrections to prevent steric clashes that have been mentioned on the
> Dock-fans list  are incorporated here.
> NEW IN DOCK 6.4
> ###Internal Energy###
> During growth and minimization, an internal energy scoring function can be
> used. The goal of the internal energy function is to reduce the occurrence of
> internal clashes during the torsional optimization. This function computes the
> repulsive Lennard-Jones term between all ligand atom pairs, excluding all 1-2,
> 1-3, and 1-4 pairs. (Currently, attractive Lennard-Jones and Coulombic terms
> are neglected; the aim is to eliminate internal clashes not to optimize the
> internal geometry. In addition, since there is no dihedral term in the force
> field, if the attractive terms are included, the molecule might appear less
> physical.) The internal energy can be cut on or off; if cut on, it is
> always used and is reported in the final energy. If it is cut off, it is never
> used. The pruning during growth is done by considering both the internal and
> interaction energies. We recommend its use.
> Note that DOCK 6.3 also had an internal energy function however it was only
> used in final minimization and not during growth.
> The modifications have greatly improved the behavior of the Anchor and Grow
> ###Growth Tree and Statistics###
> Dock uses Breadth First Search to sample the conformational space of the
> ligand. The tree is pruned at every stage of growth to remove unsuitable
> conformations. In order to be as space efficient as possible, DOCK only saves
> one level of growth at a time unless "write_growth_tree" is turned on. In
> order to construct the growth tree it was necessary to do the following: (1)
> Retain all levels of growth (before and after minimization) in memory. (2)
> Link every conformer to its parent conformer during growth. (3) While writing
> out the tree, the traversal starts from a fully grown ligand (leaf), moving up
> the branch (parent conformer) until the ligand anchor (root) is reached.
> Finally, the growth tree branch is printed as a multi-mol2 file starting from
> the anchor to the fully grown ligand, including minimizations. This newly
> implemented feature allows visualization of all stages of growth.
> Note that the growth trees can easily be visualized using the Viewdock
> module in the UCSF chimera program. Extra information regarding conformer
> number, anchor number, parent conformer, etc. can also be accessed
> directly using this tool.
> The verbose growth statistics feature is useful for debugging incomplete
> growths and other possible issues with the growth routines. This feature
> is also useful to show progress when docking larger peptide-like ligands
> (twenty or more rotatable bonds) which can take several hours.
> In the example below, cumulative timings in seconds (e.g., t=16.75s)
> are shown at the end of each line to allow quick profiling of
> the slowest steps during docking. A separate section is printed for each
> anchor sampled when using multiple anchors. For anchor #1, the orienting
> routine produces 998 orients, and 41 are retained after clustering and
> minimization. The ligand has 7 rotatable bonds. The second line shows the
> assignment of layers and segments. For details on the terminology, please
> consult the DOCK 4 paper. Subsequently, two lines of information are printed
> for each torsion sampled.
> VERBOSE GROWTH STATS : ANCHOR #1
> 41/998 anchor orients retained (max 1000) t=16.75s
> Lyr 1-1 Segs|Lyr 2-1 Segs|Lyr 3-2 Segs|Lyr 4-2 Segs|Lyr 5-1 Segs|
> Lyr:1 Seg:0 Bond:8 : Sampling 6 dihedrals C6(C.ar) C4(C.ar) C3(C.3) C1(C.3)
> Lyr:1 Seg:0 21/246 retained, Pruning: 2-outside grid 5-score 218-clustered (62 in growth tree) t=20.92s
> Lyr:2 Seg:0 Bond:5 : Sampling 3 dihedrals C4(C.ar) C3(C.3) C1(C.3) N1(N.3)
> Lyr:2 Seg:0 57/63 retained, Pruning: 1-score 5-clustered (119 in growth tree) t=22.36s
> Lyr:3 Seg:0 Bond:1 : Sampling 3 dihedrals C3(C.3) C1(C.3) N1(N.3) S1(S.o2)
> Lyr:3 Seg:0 105/171 retained, Pruning: 1-outside grid 9-score 56-clustered (224 in growth tree) t=27s
> Lyr:3 Seg:1 Bond:3 : Sampling 6 dihedrals N4(N.am) C2(C.2) C1(C.3) C3(C.3)
> Lyr:3 Seg:1 67/630 retained, Pruning: 16-score 547-clustered (291 in growth tree) t=48.8s
> Lyr:4 Seg:0 Bond:43 : Sampling 3 dihedrals C16(C.ar) S1(S.o2) N1(N.3) C1(C.3)
> Lyr:4 Seg:0 100/201 retained, Pruning: 101-clustered (391 in growth tree) t=56.67s
> Lyr:4 Seg:1 Bond:26 : Sampling 2 dihedrals C11(C.3) N4(N.am) C2(C.2) C1(C.3)
> Lyr:4 Seg:1 154/200 retained, Pruning: 13-score 33-clustered (545 in growth tree) t=73.21s
> Lyr:5 Seg:0 Bond:46 : Sampling 6 dihedrals C17(C.ar) C16(C.ar) S1(S.o2) N1(N.3)
> Lyr:5 Seg:0 99/924 retained, Pruning: 30-score 795-clustered (644 in growth tree) t=179.43s
> Lyr:1 Seg:0 indicates that this is Layer #1 and Segment #0. Layer and
> segment numbers start from zero and correspond to the array indices used
> internally. Bond:8 refers to the bond number in the mol2 file. "Sampling 6
> dihedrals C6(C.ar) C4(C.ar) C3(C.3) C1(C.3)" specifies the exact torsion
> being sampled. Six dihedral positions are being sampled in this case, as
> determined by the drive_id in flex_drive.tbl. 21/246 retained means 21
> conformers were retained from the 246 conformers generated during growth (41
> conformers x 6 dihedral positions = 246 new conformers). The Pruning section
> demonstrates how these 246-21=225 conformers were pruned: 2 conformers
> were outside the energy grid, 5 conformers exceeded the score cut-off (see
> pruning_conformer_score_cutoff) and 218 conformers were clustered. Typically
> clustering removes the greatest number of conformers during each torsion grown
> as controlled by the pruning_clustering_cutoff parameter. The reader is
> encouraged to verify that the number of conformers retained can be calculated
> as above at each stage of growth. If the growth tree is turned on, the total
> number of conformers stored in the growth tree are also reported.
> ###Database Filter###
> The Database Filter is designed for on-the-fly filtering of small molecules
> from the database during docking. Filtering small molecules by heavy atoms,
> rotatable bonds, molecular weight and formal charge is currently supported.
> This routine is designed to be modular so that other descriptors can be easily
> added. The default values are deliberately set to allow most small molecules
> to pass through. One use of this routine would be to partition a database into
> subsets such as "0-7 rotbonds" or "300-500 molwt" or "neutral charge". Another
> use would be to exclude ligands that are too small (<200 amu) or too large
> (>500 amu) for a particular target. This routine can also be used to filter a
> database without performing any docking.
> Pre-minimization, which explores only the torsional (N) degrees of freedom,
> occurs prior to standard minimization. Note that if 500 iterations of
> standard minimization and 20 iterations of torsion pre-minimization are
> specified, at most 520 steps of minimization will be performed. The motivation
> for using the torsion pre-minimizer is to optimize the torsions before
> translating. This parameter should only be used in cases where the growth tree
> reveals that the minimizer is translating a correctly oriented scaffold to
> relieve clashes instead of adjusting the torsions first. Alternatively, the
> restraint minimization routine could be used (see below).
> ###Restrained Minimization###
> We have implemented an "RMSD tether": Erestraint = k * RMSD ^ 2.
> If simplex_restraint_min is yes then every time the minimizer is called the
> conformer is restrained to the initial conformation passed to the minimizer.
> Only the active heavy atoms are used in the calculation. If this function is
> used during growth, the entered conformer grown so far is restrained including
> the most recently grown torsion. This ensures considerably less movement
> during minimization.
> The test suite now contains reference outputs from a 64 bit platform
> (x86_64). Several configuration files have been added; thanks to
> Carlos P Sosa et al. for work on the ones for the Blue Genes.
> DEPRECATED FEATURES
> 1. Elimination of the final minimization functionality from the code. We
> believe that it is no longer needed with the better behavior of Anchor and
> 2. The Internal Energy function was moved from flexible growth. The Internal
> Energy function is able to be used for all docking and minimization
> 3. For a variety of reasons still under active development,
> amber_score cannot effectively be used as a secondary_score.
> This function was temporarily deprecated in 6.1, and using input parameter
> amber_score_secondary causes program termination.
> The recommended protocol is to perform two DOCK runs with the second run
> specifying amber_score as the primary_score.
> BUG FIXES
> Some bug reports have not yet been processed, but several important bugs have
> been fixed since the last release.
> For DOCK:
> For the uses of multiple anchors fragments (choose of different portions of
> the molecule) a C++ vector was not properly cleared. This was resolved
> The orienting bug fix has been added and validated through visualization.
> The resolution of the clash problem for highly flexible ligands (Rotatable
> bonds > 7) has been accomplished by inclusion of an internal energy function
> at every stage of growth. The internal energy function can be cut on or off
> and will always or never be used, respectively.
> INPUT PARAMETER CHANGES AND THEIR DEFAULT VALUES
> use_database_filter [no] (yes, no)
> dbfilter_max_heavy_atoms  (int)
> dbfilter_min_heavy_atoms  (int)
> dbfilter_max_rot_bonds  (int)
> dbfilter_min_rot_bonds  (int)
> dbfilter_max_molwt [9999.0] (float)
> dbfilter_min_molwt [0.0] (int)
> dbfilter_max_formal_charge [10.0] (float)
> dbfilter_min_formal_charge [-10.0] (float)
> write_growth_tree [no] (yes, no)
> simplex_tors_premin_iterations  (int)
> simplex_grow_tors_premin_iterations  (int)
> simplex_restraint_min [yes] (yes, no)
> simplex_coefficient_restraint [10.0] (float)
> simplex_final_min [no] (yes, no)
> simplex_final_max_iterations  (int)
> simplex_final_min_rep_rad_scale [1.0] (float)
> simplex_final_min_add_internal [no] (yes, no)
> FILE FORMAT CHANGES
> For DOCK:
> The label for Grid Score changes from
> ########## Grid Score:
> ########## vdw:
> ########## es:
> ########## Grid Score:
> ########## Grid_vdw:
> ########## Grid_es:
> 1. http://mailman.docking.org/pipermail/dock-fans/2009-May/002058.html
> Dock-fans mailing list
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