#
# Version Stack: Latest version is on top!
# ([numbers] are FlexNovo internal reference numbers.)
#
---- Version 1.6.1 ----------------------------------------------------------
1. Bug fixes
- Fixed Corina_F license error on startup
- Availability for FlexV under windows
---- Version 1.6.0 ----------------------------------------------------------
1. Bug fixes
- serveral small fixes that are not all listed in detail
2. Computing
2.1 Ring conformation generation
2.1.1 Internal Corina: An special version of corina (www.mol-net.com)
has been compiled into this FlexX executable so that a monolithic
architecture is achieved.
2.1.2 MOE as a ring conformer generator: MOE (www.chemcomp.com) can now
be used to perform the ring conformer computation. This needs an SVL
script which is part of the release package.
3. Menus and user interface
3.1 New command: PLACING/READFCOORD
Reference coordinates will be loaded from a MOL2 file and will be assigned
on the basis of subgraph matching. The reference coordinates of the subgraph
can be used to place fragments manually.
3.2 New command: PLACING/SCORE
Placements of fragments will be computed in order to generate a scoring table,
which can be used for the command PLACING/INIT.
4. File formats
5. Graphics
6. Misc.
Added the fragment space "KnowledgeSpace" to the examples.
7. Documentation
---- Version 1.5.0 ----------------------------------------------------------
1. Bug fixes
2. Computing
- new base placement algorithm: single interaction scan (SIS).
This new algorithm can be used with the new option 1 of PLACING/PLACE
3. Menus and user interface
4. File formats
- Direct import of a receptor MOL2 file (no RDF file needed).
This feature was completly revised, however there is still
a known issue: under certain circumstances (e.g. large protein
structures) reading proteins in mol2 format might last very
long, especially if no active site is defined in the mol2
input file.
We are still working on this problem!!
5. Graphics
6. Misc.
7. Documentation
---- Version 1.4.2 ----------------------------------------------------------
1. Bug fixes
- Fixed a bug in the fragment initialization routine, which led to
inconsistencies in some special cases, for instance, when filtering and
placing fragments.
- Fixed a bug in the calculation of enclosing spheres that occurred when
estimating the volume of partial solutions. This led to numerical
instabilities and assertion failures later on.
- Fixed a bug in the treatment of partial solutions where the removal failed
in some rare special cases. This led to a failed assertion later on.
2. Computing
3. Menus and user interface
4. File formats
5. Graphics
6. Misc.
7. Documentation
---- Version 1.4.0 ----------------------------------------------------------
1. Bug fixes
- Fixed a bug in the temporary file generation where a check was missing if
the user is allowed to actually access an already existing file. Before,
the subsequent generation of all temporary files failed.
- Fixed a bug in the handling of the molar refractivity values. The filter
did not check whether or not a range for mol_refrac was provided in the
specification, which resulted in wrongly discarded fragments/solutions.
- Fixed a bug in the PLACING/SELECT command where a check was missing for
the 'best # mode' if any scores were annotated at all. This led to a failed
assertion later on.
- Fixed a number of (minor) bugs and special cases that occurred during
transfer, counting, and loading of placements.
- Fixed a bug when writing fragments or solutions in SD format that led to
program crashes before.
2. Computing
- A 'complete' pharmacophore definition can now be used during the build-up
calculation. The specification of the pharmacophore has to be done in
such a way, that the algorithm is able to iteratively fulfill one or more
additional constraints in each fragment addition step, i.e. in each
extension cycle. Naturally, all final solutions are checked against the
complete pharmacophore definition.
Note that logical expressions cannot be used in this context.
- The 3DGENERATOR program can now be used. It generates low-energy (input)
coordinates during the initialization of fragments and partial solutions.
If the corresponding flag 3D_GEN is set to 2 (default), the program will
try to correct the coordinates if the fragment is self-overlapping. If the
value of the flag is set to 1, EVERY fragment and solution that is
generated will be processed, which will result in a huge increase in
computation time. If the flag is set to 0, the program will not be used.
- There are now the manual and perturbation modes available for the
placing of fragments. These modes work correctly only if the coordinates of
the corresponding fragment(s) are already within the active site of the
receptor. The algorithm then generates a single (manual) or a low number
(perturbate) of sampled start placements for the fragment(s) that are
derived from the input coordinates. These can then be used as start
placement(s)s for the build-up calculation.
- The SIS base placement algorithm is now available. It will be used
automatically during the fragment placing if no solution could be obtained
by either of the triangle (mode 3) or the line (mode 2) modes. It can also
be selected explicitly (mode 1) by the user.
3. Menus and user interface
- When writing fragments or flexnovo solutions to disk there is now a default
value for the coordinate selection given and used, in case the user does
not provide one. Before nothing happened and an error message was printed.
4. File formats
- Improved the support for output in SD format a little.
5. Graphics
6. Misc.
- Increased the default value for the NOF_PLACEMENTS parameter in the
flexnovo settings file in order to better account for the more fine-grained
torsional sampling of links, which is a result of an earlier bug fix.
Depending on the size of the fragment space, this may increase runtime.
7. Documentation
---- Version 1.3.6 ----------------------------------------------------------
1. Bug fixes
- Fixed an error in the ranking of fragment placements that led to
instabilities in the sorting function in case two placements cannot be
distinguished from each other by (dock_entry) key values. [186]
- Fixed a bug in the clustering of fragment placements that led to a
very coarse-grained sampling with respect to the torsional angles retained
at the end. Additionally, for intermediate solutions of the build-up
algorithm, the larger RMS value is now used for clustering. [187]
- Added some more consistency checks for the fragment space file parser
that now checks also for the definition of the link compatibility matrix.
2. Computing
- Significantly improved the treatment of dummy/link atoms:
The assignment of sybyl atom types and vdW-volumes for links is now more
consistent, especially with respect to the TEST_ATOM_TYPES flag in the
config.dat file and the values specified in the champar.dat file.
3. Menus and user interface
- The build-up function now prints also a summary in case there are no
extendable solutions found in an extension cycle.
4. File formats
- Increased the radii of dummy atoms in the chempar.dat file to the size
of a hydrogen atom. Fixed also an error in the specification of sybyl
atom types (table @atom_types) for dummy atoms.
5. Graphics
6. Misc.
7. Documentation
---- Version 1.3.5 ----------------------------------------------------------
1. Bug fixes
- Fixed a bug in the processing of the reference fragments. These were
extended in the 'wrong' order according to the score, i.e., from low
scores to high ones, instead of from high scores to low ones.
- Fixed a bug that occured upon transferring partial solutions. In some
cases, the matches were not transferred correctly so that one match
would be missed and the other would be counted twice. This led also to
different scores of the transferred solution. Additionally, the first set
of coordinates of the reference was transferred twice to the target, and
the last coordinate set of the reference was therefore discarded. This
bug is also fixed now [185]
- Fixed a bug in the build-up algorithm where inclusion SMARTS pattern were
applied to intermediate results instead of to final results only.
- Fixed a bug in the calculation of the build-up statistics where the
amount of placements generated was not counted correctly in some cases.
- The buriedness and saturation placement filter functions were not checked
correctly when carrying out the second step of the fragment placement
algorithm. Also some small memory leaks occured when using these filter
functions together with pharmacophore-type constraints.
- Fixed some minor errors that could result in small memory leaks in some
special cases.
- Improved robustness of fragment space and filter format file parser and
added additional consistency checks.
2. Computing
3. Menus and user interface
- Adjusted the amount of output of the build-up algorithm for higher
verbosity levels.
- Improved the error handling and modified the output a little when loading
in pharmacophore-type constraints.
- new flag USE_ACCESS_SCALING for turning on and off access scaling.
4. File formats
- Chempar.dat is splitted in two parts:
- the new chempar.dat with the general chemistry knowledge (CHEMPAR)
- flexnovo_settings.dat with tool specified parameters (SETTINGS)
- Changed two identifier in the fragment space file (fsf) for consistency:
@link_terminals => @link_terminal_groups
@link_connects => @link_compatibility_matrix
- Added additional warnings and error messages for missing or wrong
specifications in the fragment space file
5. Graphics
- Fixed the annotation of match energies when drawing placements for
fragments or build-up solutions.
6. Misc.
- New programm parameter 'LOGP_CLASS' is added:
- LOGP_CLASS = 1 : Wildmann/Crippen descriptors
- LOGP_CLASS = 2 : Ghose/Crippen descriptors
7. Documentation
---- Version 1.3.1 ----------------------------------------------------------
1. Bug fixes
- Fixed a bug in the creation of the initial fragment queue for the build-up
calculation: In case a fragment was skipped because an identical fragment
was already inserted in the queue, the remaining fragments were not
processed correctly. [96]
- Fixed the handling of a special case in the geometry calculations when
connecting fragments. This led to a fatal error before. [107]
- Fixed some output inconsistencies for verbosity levels lower than 4
- Improved robustness of fragment space and filter format file parser
- Fixed the output of the LIGAND INFO command where some special characters
accidentaly appeared when writing the output into a file
- Fixed a bug where the number of R/S and E/Z stereo centers was swapped in
the output of LIGAND/INFO, FRAGSPACE/FINFO and BUILDUP/SOLINFO commands
- Fixed a bug where a ligand was not converted from a SMILES string if the
flag 3D_GEN was not set to 1.
- Improved the functionality and concistency of the CHECK function for
detecting possible configurational changes if Nitrogens upon fragment
connection or link substitution, which cannot be accounted for during
the build-up algorithm (see also tutorial in the user guide).
- Fixed a uniqe bug that occured in a special case in the build-up algorithm
during the calculation enclosing spheres of components. [124,144]
- Fixed a bug in the internal handling of large SMARTS expressions
2. Computing
3. Menus and user interface
- Added additional warnings and error messages for missing or wrong
specifications in the fragment space file
4. File formats
5. Graphics
6. Misc.
7. Documentation
---- Version 1.3.0 ----------------------------------------------------------
1. Bug fixes
- Fixed some path handling problems in case the default path has to be used
- Fixed more errors in the handling of filter expressions during the build-up
algorithm. These were not checked for molecules in some special cases.
- Fixed a bug in the calculation of molar refractivity values that occured
for a special parametrization, which is different from the one used by
default.
2. Computing
- There is a new placement filter available (FILTER_OUT_OF_SITE), which
prevents the algorithm from generating poses where heavy atoms of the
fragment are placed outside of a sphere enclosing all active site atoms.
- The number of rotatable bonds is now calculated according to the Boehm
scoring function definition, meaning as the number of acyclic, non-terminal
bonds between atoms with SP3 hybridisation.
- Filter SMARTS expressions are now checked during the build-up calculation
as well. Please keep in mind that this can be very time-consuming,
depending on the type and length of the exclusion/inclusion SMARTS lists.
3. Menus and user interface
- The LIGAND menu (known from FlexX) is now included in the program.
Reference ligands can now be loaded, visualized and be used, for example,
for the definition of protein active sites. The TRANSFORM functions are
not available though.
- There are now functions available for drawing fragments and placements.
New commands MDRAW in submenus FRAGSPACE, PLACING and BUILDUP.
Each of them has its own drawing context so that default values can be
set in the corresponding graphic.dat static data file or via the menu.
New commands SELGRA, SELCOL, SELADM, SELLAB and GRAINF in the submenus
FRAGSPACE, PLACING and BUILDUP.
- There are now functions available for listing placement and matches
information. New commands LISTALL, LISTPLM, LISTMAT, LISTONE in submenus
PLACING and BUILDUP. Each of them prints a table of the corresponding
data from an internal database (as known from FlexX). Additionally,
custom SQL-like queries can be used via the command QUERY and QHIST.
- A global HELP command is now available for functions, which prints syntax
descriptions of all commands available.
4. File formats
5. Graphics
- Default graphic context settings for fragments and placements are now
included in the static data file graphic.dat. They can be altered in the
file directly, or via the corresponding menu commands (see above).
6. Misc.
- FlexNovo now has its own chempar.dat file.
- FlexNovo is now based on a fully reworked and improved code library.
- FlexNovo is now available for Linux and Linux 64bit architectures.
The 64bit version improves the performance of the program up to 30% but
uses significantly (about 30%) more memory at the same time.
7. Documentation
- a complete user guide is now included in the package
- for a detailed description of the new commands available please refer to
the user guide and/or use the new internal help command!
---- Version 1.2.6 ----------------------------------------------------------
1. Bug fixes
- Fixed a segfault when reading a filter definition file without having a
fragment space loaded previously.
- Filter SMARTS expressions were not separated correctly in case inclusion
and exclusion SMARTS were used at the same time.
- The PLACING/SELECT command had the wrong upper limit when selecting the
best scoring # of fragments.
- Fixed an error in the handling of logical expressions for pharmacophore
type constraints. Placements fulfilling the constraints were wrongly
discarded in some cases. [49]
- Fixed an error that occurred when a pharmacophore was loaded and the
build-up algorithm was started without deleting the pharmacophore
beforehand. [51]
- Fixed an error that occurred in a special case when loading placement files
and resulted in a floating point exception. [50]
- Fixed an error in the handling of filter expressions during the build-up
algorithm. These were not checked for the reference fragments before
putting them in the final solution list.
2. Computing
3. Menus and user interface
- The FRAGSPACE/FINFO command now prints PSAS instead of SAS.
4. File formats
5. Graphics
6. Misc.
7. Documentation
---- Version 1.2.5 ----------------------------------------------------------
1. Bug fixes
- Segfault when filtering fragments is now fixed.
- The function FRAGSPACE/READ now checks for redundant entries in the fsf
file and handles such cases consistently. This lead to a segfault in
some cases before.
2. Computing
- The build-up algorithm now stops immediately if no start fragments are
selected or no placements are available.
3. Menus and user interface
- New command PLACING/FLIST, which prints a list of fragments with their
corresponding initialized score and best placement score, if available.
- The command PLACING/INFO now prints seperators between fragments for
table format output.
4. File formats
- Changed two filter identifier for consistency reasons:
'psa' is now 'psas', 'ringystems' is now 'rings'.
5. Graphics
6. Misc.
- the CLASH_FACTOR default value changed from 0.6 to 0.7 in order to avoid
fragment combinations having strained conformations in some cases.
- all placement geometry filter functions are activated by default.
7. Documentation
- this file now contains a summary of the changes made recently.
- syncronized standard parameters in the user guide with static data.
- corrected description of filter functionality.
---- Version 1.2.2 ----------------------------------------------------------
1. Bug fixes
2. Computing
- A new fragment initialization function is used, which is different with
respect to the FlexX initialization. In particular, no TRANSFORM expressions
can be used.
- Identical build-up solutions are now identified and filtered using USMILES
Link atoms are identified and treated consistently in the USMILES string.
3. Menus and user interface
- The existence of placement files is now checked before initializing a
fragment.
4. File formats
- Fragments and build-up results can now be exported as mol, sln or pdb file.
Additionaly, coordinate sets can be written to a single or multiple files.
- Updated placement description file format.
- Changed parameters PDF_FORMAT to PDF_COMPRESSION and CFSPACE to FRAGSPACE
for consistency reasons.
- the static data files are now encrypted by default.
5. Graphics
6. Misc.
- FlexNovo now is a stand-alone program.
7. Documentation
- Updated short help files.
- Updated the user guide.
---- Version 1.2.0 ----------------------------------------------------------
1. Bug fixes
- Removed obsolete warning messages for the log P calculation
- Fixed some directory path managing problems.
- Placement information is now correctly deleted from memory in case only
the score info is written to a file.
- Link atoms are now resolved correctly in some special cases.
- SMILES strings for terminal group definition were not used correctly in
case of double or triple bonds.
- The PLACING/SELECT command now works correctly.
2. Computing
- Basic placement information can now be written to a file directly during
the placement calculation.
- Pharmacophore definitions with logical expressions can now be used
3. Menus and user interface
- New command PLACING/INFO which prints basic placement information
- New command PLACING/INIT which reads fragment scores from a file that are
used later as score estimation in the build-up calculation.
- New command FRAGSPACE/CHECK which checks if fragment geometries and the
connection rules defined are compatible to each other.
- Adjusted the amount of output the program gives for different verbosity
levels.
4. File formats
- The placement description files (pdf) are encoded using the fragment
sybyl name only.
- The placement description files can now be written in gzip format as well
instead of plain text only before.
- The argument list for a batch script now uses additionally %{} instead of
$() before. This circumvents shell escaping problems for different setups.
5. Graphics
6. Misc.
- FlexNovo is now based on the FlexX Release 2 Kernel.
7. Documentation
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