DOCK 6.11

This is a release of the version with the new descriptor-driven de novo design
method DOCK_D3N.  DOCK_D3N takes advantage of the integration of DOCK6 and RDKit
as presented in reference [1].


NEW IN DOCK 6.11

Enhanced DOCK_DN routine (DOCK_D3N)
    New feature includes the integration of the open-source toolkit RDKit with
    the DOCK6 codebase, allowing users to calculate important drug-based
    descriptors for molecules. On top of the ability to calculate these
    descriptors, DOCK6.11 include an enhanced version of DOCK_DN, termed
    "descriptor-driven de novo design" (DOCK_D3N). This method allows users to
    specify descriptors (and their target ranges) to bias the on-the-fly
    molecular construction.  This powerful and flexible routine tailors ligand
    growth towards desirable regions of chemical space.

Integration of RDKit and DOCK
    In DOCK6.11, compilation infrastructure is developed to download and compile
    RDKit to eventually compile with DOCK. This enables DOCK to interface
    with various features in RDKit.  For consistency with reference [1], this
    installation mechanism uses RDKit Release 2019.09.1 which depends on
    Boost 1.71.0 and Eigen 3.3.9.

Calculation of cheminformatic descriptors
    RDKit is utilized in a wide array of DOCK features to calculate
    descriptors for resulting molecules (DOCK_GA, Database Filtering,
    Rigid/Flexible Docking).

Miscellaneous
    Incremental improvements in documentation, installation, and testing.
    Configuration files for GNU compilers installed on macOS using the
    Homebrew package manager have been added.  These cater to idiosyncratic
    details of environment's, and it may be the case that the general gnu set
    of DOCK configuration files work fine on your mac.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

BUG FIXES

For DOCK:

    1. In DOCK_DN, not all dumped pruned molecules were not being written in an
       output mol2 file due to deactivated molecules.  Reactivation of molecules
       were added to fix this.

    2. In DOCK_DN/GA, DOCK will check if the VDW input parameter file is correct.


~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

INPUT PARAMETER CHANGES AND THEIR DEFAULT VALUES

Example:
    parameter_name                      [default_value] (options):


Added:

For DOCK_DN:
    dn_drive_verbose                     [no]                          (yes,no):
    dn_drive_clogp                       [no]                          (yes,no):
    dn_lower_clogp                       [-0.30]                       ():
    dn_upper_clogp                       [3.75]                        ():
    dn_clogp_std_dev                     [2.02]                        ():
    dn_drive_esol                        [no]                          (yes,no):
    dn_lower_esol                        [-5.23]                       ():
    dn_upper_esol                        [-1.35]                       ():
    dn_esol_std_dev                      [1.94]                        ():
    dn_drive_tpsa                        [no]                          (yes,no):
    dn_lower_tpsa                        [28.53]                       ():
    dn_upper_tpsa                        [113.20]                      ():
    dn_tpsa_std_dev                      [42.33]                       ():
    dn_drive_qed                         [no]                          (yes,no):
    dn_lower_qed                         [0.61]                        ():
    dn_qed_std_dev                       [0.19]                        ():
    dn_drive_sa                          [no]                          (yes,no):
    dn_upper_sa                          [3.34]                        ():
    dn_sa_std_dev                        [0.9]                         ():
    dn_drive_stereocenters               [no]                          (yes,no):
    dn_upper_stereocenter                [2]                           ():
    dn_drive_pains                       [no]                          (yes,no):
    dn_upper_pains                       [1]                           ():
    dn_start_at_layer                    [1]                           ():
    sa_fraglib_path                      [sa_fraglib.dat]              ():
    PAINS_path                           [pains_table_2019_09_01.dat]  ():

For Database Filter:
    dbfilter_max_stereocenters           [6]                           ():
    dbfilter_min_stereocenters           [0]                           ():
    dbfilter_max_spiro_centers           [6]                           ():
    dbfilter_min_spiro_centers           [0]                           ():
    dbfilter_max_clogp                   [20]                          ():
    dbfilter_min_clogp                   [-20]                         ():
    dbfilter_max_logs                    [20]                          ():
    dbfilter_min_logs                    [-20]                         ():
    dbfilter_max_tpsa                    [1000.0]                      ():
    dbfilter_min_tpsa                    [0.0]                         ():
    dbfilter_max_qed                     [1.0]                         ():
    dbfilter_min_qed                     [0.0]                         ():
    dbfilter_max_sa                      [10]                          ():
    dbfilter_min_sa                      [1]                           ():
    dbfilter_max_pns                     [100]                         ():
    filter_sa_fraglib_path               [sa_fraglib.dat]              ():
    filter_PAINS_path                    [pains_table_2019_09_01.dat]  ():

For DOCK_GA:
    sa_fraglib_path                      [sa_fraglib.dat]              ():
    PAINS_path                           [pains_table_2019_09_01.dat]  ():


~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

OUTPUT COMPONENTS

For DOCK_D3N:
    1. ${output}.denovo_rejected.mol2 is the mol2 file containing the
       partially/complete molecules by D3N. Whenever molecules are outside of
       the user-defined ranges shown in the table above, molecules will go here.
       (This file is created, when "dn_save_all_molecules" is turned on. )

For Database Filter:
    1. ${output}.rejected.mol2 is the mol2 file containing scored molecules
       that got rejected by dbfilter.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

KNOWN BUGS

    1. When selecting both internal energy and internal energy score, the
       parameter "internal_energy_rep_exp" appears twice in the question tree,
       and it will be queried during user input when DOCK is invoked from the
       command-line even if the value is already set.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

RELEASE DATE

November 2023

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

REFERENCES

1. Matos G.D.R; Pak S.; Rizzo, R.C.  Descriptor-Driven de Novo Design
Algorithms for DOCK6 Using RDKit.  J. Chem. Inf. Model., 63(18): 5803-5822,
2023.  https://doi.org/10.1021/acs.jcim.3c01031