Solutions for Cheminformatics

1

• Solutions for Cheminformatics

Migration from ISIS environment
Szabolcs Csepregi et al
November 2008
2
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

3
Product Map
4
ChemAxon Embedded - examples

• Workflow
• Pipeline Pilot, Inforsense, and KNIME.
• ELN
• Agilent, Contur, DeltaSoft, Kinematic, etc.
• SAR
• Spotfire, Synaptic Science, Omniviz
• Databases
• Aureus, GVK, Jubilant Biosys, Patcore
• Web
• Thomson Reuters, Wiley, Houghton Mifflin,
  Cengage, Prentice Hall, Collaborative Drug
  Discovery, RCSB PDB, BindingDB, NIH/NLM
  ChemIDPlus, Molport etc

5
The Marvin family
MarvinSketch/View http//www.chemaxon.com/MarvinSk
etch_View.ppt MarvinSpace http//www.chemaxon
.com/MarvinSpace.ppt
MarvinSketch MarvinView MarvinSpace
Available as Java applets for HTML pages and Java
beans for standalone apps (full API)
Publication quality macromolecule visualization
Individual and structure table visualization
Structure, query reaction editing
6
Marvin Development History
2000
1999
2001
2003
2002
1998
SMILES, SMARTS, PDB, Rgroups, isotopes,
shortcuts, Marvin Beans
Ball and stickJPG, PNG, SVG, CutPaste with
Isis/ChemDraw, 2D cleaning, (de)aromatization,
reaction drawing
SDF, RDF, XYZ animations, CML, templates,
compressed formats, Swing, 3D models
Applets, Molfiles, stereo support, Windows, Unix
Mac support, signed applets, Java Web Start, atom
mapping
Partial charge, pKa, logP/logD,3D optimization,
radicals,abbreviated groups
2008
2007
2006
2004
2005
Tautomers, resonance, lone pairs, conformers, 3D
sketching, MarvinSpace, Topology analysis,
presentation quality graphics,...
More Plugins, more R-groups, EMF, PDF and
Mol2, Improved property storage in MRV, SDfiles
and Rdfiles. .NET support in MarvinBeans.
Name to structure, OLE 2, Chemical
Terms Customizable GUI
Marvin file format, enhanced stereo, shapes, text
boxes, multiple groups, link nodes, TPSA,
recursive SMARTS, Donor/Acceptor, electron
arrows,
Structure to name, Coordination compounds,
Polymer drawing, OLE, Markush enumeration
plugin Configurations
7
Calculator Plugins
Calculator Plugins http//www.chemaxon.com/Calcula
tor_Plugins.ppt
A variety of structure based calculations are
available from the Marvin GUI, cxcalc command
line tool and the API. The calculations are
widely used within several JChem tools and are
available as functions of Chemical Terms
expressions.
Elemental Analysis IUPAC Name Standard IUPAC
Name Protonation pKa, Major Microspecies,
Isoelectric Point Partitioning logP,
logD Charge Charge, Polarizability, Orbital
Electronegativity Isomers Tautomerization,
Resonance, Stereoisomer Conformation Conformer,
Molecular Dynamics Geometry Topology Analysis,
Geometry, Polar Surface Area (2D), Molecular
Surface Area (3D) Markush enumeration Other Hyd
rogen Bond Donor-Acceptor, Huckel Analysis,
Refractivity
8
Chemical Naming

• Structure to Name/ Name to structure
• Supported nomenclatures
• Chains, Monocycles/ Traditional names with and
  without heteroatom/ Spiro ring systems/ Ethers/
  Common characteristic groups, Ionic compounds/
  Unlimited number of atoms and rings/ All atom
  types /Stereochemistry/ etc.
• Usage
• dragdrop or copypaste to MarvinSketch
• Label updated in real-time
• Automatic format recognition
• Batch from command line

9
JChem family
10
JChem development history
2000
2002
2001
2003
2004
Oracle, MySQL, SQLServer, Access, hashed
fingerprints, substructure and similarity search
DB2, PostgreSQL, Rgroup searching
Reaction searching, fragmentation, reaction
processing, standardization, pharmacophores,
screening
Clustering, diversity
Cartridge, enhanced stereo searching, recursive
SMARTS, Chemical Terms, virtual synthesis
2005
2006
2008
2007

• Position variation queries,
• Instant JChem
• - Federated search,
• - Cartridge support...
• JChem for Excel

R-decomposition,R-enumeration, reaction library,
custom fingerprints, random synthesis, link nodes
Tautomer search, Instant JChem reaction
similarity, Library MCS, GUI for Standardizer/
Reactor
Calculated columns, Installer, Tautomer Duplicate
filtering, Query tables, Markush tables, Speed
enhancements for JChem Cartridge, form design,
relational data for Instant JChem ...
11
JChem Base
Structural Search http//www.chemaxon.com/Structur
al_Search.ppt JChem Base http//www.chemaxon.com/J
Chem_Base.ppt

• Features
• Fast and sophisticated searching(chemical and
  non-chemical data, Chemical Terms filter, many
  options)
• Custom standardization
• Calculated columns
• Combinatorial Markush structure tables
• Interfaces
• Integration with most relational database engines
• JChem Cartridge for tight Oracle SQL integration
• JSP integration open source web example
• Desktop-ready through Instant JChem

12
Searching in combinatorial Markush structures

• Combinatorial Markush structure registration and
  search
• Markush features handled in search
  enumeration
• R-groups (nesting to any depth)
• Atom lists, bond lists
• Position variation bond
• Link nodes
• Compatible Markush enumeration plugin
• Not all query features supported
• Detailed description
• http//www.chemaxon.com/product/markush_search.htm
  l

13
JChem Cartridge for Oracle
JChem Cartridge http//www.chemaxon.com/JChem_Cart
ridge.ppt

• Access JChem functionality via SQL functions
• All search features of JChem Base
• JChem index for chemical data in arbitrary
  database structure
• Chemical filters and property predictors using
  Chemical Terms
• Standardization (structure canonicalization)
  during registration
• Structure format conversions
• 2D, 3D image generation
• Library enumeration using virtual reactions and
  Markush structures

14
Instant JChem
Instant JChem http//www.chemaxon.com/conf/Instan
t_JChem.ppt
Desktop application for local and remote chemical
database management, search and structure based
prediction

• Simply connect to external databases and share
  your native database simultaneously
• Powerful search functionalities
• Scalable explore large datasets (106 )
• Dynamically predict properties using Calculator
  Plugins
• Apply canonicalization rules for import and
  viewing
• Wide import / export options
• Merge data sets into a single set
• Very active development what do you want to do?

15
JChem for Excel

• Microsoft Excel integrated solution for Marvin
  and JChem functionality
• Use Excels powerful features Functions,
  Sorting, Filtering, Charts
• Implemented in C .NET, and Visual Studio
• Proof that ChemAxon APIs can be used in a
  Java-less .NET environment
• Easy to install and deploy
• UNDER DEVELOPMENT

16
Canonicalization with Standardizer
Standardizer http//www.chemaxon.com/Standardizer.
ppt

• Structure canonicalization
• Mesomers
• Tautomers
• Solvent and counter ion removal
• Aromatization, dearomatization
• Explicit/implicit hydrogen conversion
• Stoichiometry expansion
• Stereo manipulations
• 2D cleaning
• Template based cleaning
• Custom rules
• Availability
• JChem Base, Cartridge IJC
• API (Java and .NET)
• Batch processing
• GUI

17
Drug discovery tools
18
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

19
Contents

• A short introduction of JChem Cartridge
• MDL/Symyx features in JChem
• Migration from MDL/Direct and ISIS/Host
• Migration case studies and user feedback

20
Purpose of JChem Cartridge

• Access JChem functionality using SQL
• SELECT count() FROM nci WHERE jc_contains(structu
  re, 'Brc1cnc2ccccc12') 1
• Access JChem in any programming environment
  offering Oracle connectivity (.NET, Java, Perl,
  PHP, Python, Apache mod_plsql...)?
• Execute SQL queries efficiently using extensible
  indexes
• Precompute chemical information on structures by
  creating jc_idxtype indexes
• CREATE INDEX jcxnci ON nci(structure) INDEXTYPE
  IS jc_idxtype
• The jc_idxtype implementation scans the indexed
  column for eligible structures in one single
  performance-optimized operation domain index scan

21
Features of JChem Cartridge

• Adds chemistry knowledge into the SQL language of
  Oracle (SELECT, INSERT, UPDATE, ...)?
• Substructure, superstructure, exact structure,
  similarity searching
• Fast typically 10k hits in 3M structures within
  a second
• Complex chemical expressions using the Chemical
  Terms language that includes logP, pKa, ...
• Automatic property calculation during
  registration
• Standardization (canonicalization) during
  registration
• Structure format conversions (MRV, Molfile,
  SDfile, RDfile, SMILES, CML, etc.)?
• 2D, 3D image generation
• Structure enumeration using reaction rules
• Interaction with Oracle optimizer

22
Operators and functions

• jc_compare substructure/similarity/exact
  searching combined with Chemical Terms
  expressions
• jc_matchcount number of occurences of the query
  structure in the target
• jc_evaluate Chemical Terms evaluation
• jc_molweight molecular weight
• jc_formula molecular formula
• jc_react structure enumeration based on virtual
  reactions
• jc_standardize structure canonization
• jc_molconvert conversion to different formats
  (image generation is supported)
• jc_tanimoto similarity search
• jcf.hitColorAndAlign substructure coloring and
  alignment
• Similarity search example displaying ID, SMILES
  code, and molweight
• SELECT cd_id, cd_smiles, cd_molweight FROM
  my_structuresWHERE jc_tanimoto(cd_smiles,
  'CC(O)Oc1ccccc1C(O)O') gt 0.8

23
Structure search features

• Wide range of query atoms
• Query properties
• R-group queries
• Full SMARTS support
• Coordination compounds
• Link nodes
• Position variation
• Pseudo atoms
• Lone pairs
• Relative stereo
• Reaction search features
• Hit coloring

See detailed information on structure search
www.chemaxon.com/conf/Structural_Search.ppt
24
Search options

• Chemical Terms filter constraint
• Tautomer search
• sp hybridization state check
• Stereo on/off
• Ignore charge/isotope/radical/valence/mixture
  brackets
• Vague bond matching modes or aromatic ignore
  bond types
• Inverse hit list
• Maximum search time / number of hits
• SQL SELECT statement for pre-filtering
• Ordering of results
• etc.

25
Compatibility and integration

• File formats
• SMILES
• MDL molfile (v2000 and v3000)
• MDL SDF
• RXN
• RDF
• MRV
• IUPAC name, InChI

• Operating systems
• Windows
• Linux
• Solaris
• HP-UX
• etc.

DB engines Oracle versions 9i R2 or above for
alternative RDBMS systems, see the JChem
Base presentation http//www.chemaxon.com/JChem
_Base.ppt
26
Index parameters

• Index parameters affect
• Fingerprint attributes
• Standardizer configuration
• Table space and storage options of the index
  table
• Examples
• Standardization by stripping hydrogens and using
  basic aromatization
• CREATE INDEX jcxnci ON nci(structure) INDEXTYPE
  IS jc_idxtype PARAMETERS('STD_CONFIGdehydrogenize
  optional..aromatizeb')?
• Add structural keys to fingerprint for more
  efficient substructure searching (structural keys
  are defined in table stfp_keys)
• CREATE INDEX jcxnci ON nci(structure) INDEXTYPE
  IS jc_idxtype PARAMETERS('STRUCTURALFP_CONFIGsele
  ct structure from stfp_keys')?

27
Supported Column Types

• VARCHAR2 typically for short formats, e.g.
  SMILES
• CLOB
• BLOB

for longer formats, e.g. MDL molfile, Marvin
(mrv)
28
MDL Feature Compatibility
The learning curve of chemists familiar with ISIS
is very short. After having some practice, Marvin
is reported a more productive drawing
environment. The most of the MDL features are
available in Marvin and JChem, and many others
not available in MDL technology.

• Generic atom types and bond types
• Atom query properties
• Atom Lists/ not lists
• Aliases
• Pseudo atoms
• Atom values
• Group and brackets
• Abbreviated groups
• Multiple groups
• Repeating units
• Polimers
• Mixtures
• Attached Data

• Link Nodes
• R-groups, R-logic
• Stereochemistry
• Chiral flag
• Parity
• Double bond stereo
• Enhanced stereo (abs/end/or)
• inv/ret
• Reacting center on bonds
• Reaction mapping
• Topology (ring/chain)
• Option for ISIS-like look
• Others

29
MDL Feature Compatibility
What is missing

• Polymer search (coming in 5.2)
• Attached data S-group search (coming in 5.2)
• 3D special features
• Exact change flag (reaction)

30
Migration from MDL/Direct cartridge

• 2 alternatives
• JChem indexes need to be created on structure
  columns of existing tables, or
• Structural data migrated to new tables with JChem
  Cartridge indexes
• The MDL/Direct SQL operators need to be changed
  to JChem operators in all uses.
• Non-chemistry tables no need for migration

31
Migration from ISIS/Host

• Molecule source need to be accessible for JChem
• Through exporting SD/Rdfiles from ISIS and
  importing into new tables with JChem index, or
• Setting option in ISIS/Host to include molfile in
  RCG tables, and
• Use SQL to insert mol field into JChem tables, or
• Add JChem index on original tables
• ISIS/Host interfaces need to be rewritten to use
  SQL only, referencing JChem operators.
• Hviews and GUI-s need to be replaced separately.
  (See further slides later.)
• Non-chemistry tables no need for migration

32
An Independent Comparison

• FMC migrated from MDL ISIS/Base ISIS/Host to
  ChemAxons JChem. They later published their
  detailed scientific comparison.
• Used 1.8 million vendor compounds to create a
  testing database
• Prepared 115 different query structures for
  comparison
• 51 simple sub-structure search
• 51 similarity search
• 64 complex search
• Identical search hits in almost all cases, major
  differences result from MDLs incorrect aromatic
  bond definitions in case of 5 member aromatic
  rings. ChemAxon's approach is the chemically
  correct and their performance is higher (faster).

33
Identical Results
34
Differences
35
Vague Bonds

• For the sake of perfect compatibility with MDL
  searching ChemAxon provides vague bond options to
  retrieve results according to MDL systems.

36
Technical Comparison

• Supported Platforms
• ISIS Sun Solaris, Windows Servers
• JChem Sun Solaris, Windows Servers, Linux, Irix,
  MAC
• Supported Databases
• ISIS Oracle
• JChem Oracle, MySQL, SQL Server, PostgreSQL,
  Access, DB2
• Processing SD Files
• ISIS 31 hours, Pipeline Pilot ISIS
• JChem 11 hours, JChem
• Technology Transparency
• ISIS Unclear Data/Table Structures
• JChem Clear Understanding of
• Flow of Data
• Structure of Data
• Execution Process
• Native Oracle Tables and Procedures
• Performance
• ISIS Slow similarity search
• JChem Fast similarity search

37
Comparison Conclusions

• Technical Conclusion
• Clear and straightforward understanding of data
  representation and system architecture
• Integrated system
• Quicker and less error-prone
• Less hassle for software development
• From technical point of view, ChemAxon is
  favorable
• Business Conclusion
• ChemAxon was the better choice

38
Migration Experience Questionnaire

• Five companies were interviewed about their JChem
  Cartridge migration experiences in the form of a
  questionnaire containing 14 questions.
• A UK based service/biotech company
• A Swedish biotech company
• A US branch of a Swiss pharmaceutical company
• A Japanese pharmaceutical company
• A US branch of a Japanese pharmaceutical company

39
Migration Experience

• 1. What was the platform you used before the
  migration?
• All systems were run using the Daycart cartridge
  on Linux servers
• MDL Cartridge running on Sun Solaris
• Daycart
• We used ISIS/Host as a server, the client was
  ISIS/Base customized using ISIS/PL
• Daylight and IDBS Chembridge
• 2. How long did it take to migrate?
• Very simple, hardly any time at all, just a few
  hours to uninstall old cartridge, install new
  cartridge and build indexes. Then modify a few
  SQL statements in the code to use the new
  cartridge functions.
• It took a full weekend to switch over and convert
  all old databases.
• Since we use SQL for structure searches, the
  actually change in the application code are few.
  Code changes takes about 1 day. However, we spent
  at least two weeks to compare the daylight and
  jcart.
• It took 1 year for planning, and another 1 year
  for designing and developing the system.
  1-year-migration time includes all of the
  operation that is needed. That means our
  technical people worked for this project 1 year.
  We migrated the data structure of HView, but the
  form was re-designed in order to fit our existing
  (wet) workflow.
• Two months

40
Migration Experience

• 3. How many technical people were required in the
  migration process?
• It was fairly simple so just one developer with
  all round programming, database, and chemistry
  knowledge.
• One person
• 2 people
• 6 technical people. 2 were contacting with users.
  For the system design, 11 users were involved
  from chemistry, HTS, eADME groups.
• 1.5
• 4. Why did you decide on leaving the previous
  platform? (problems)
• Purely the cost. We found the Daycart system to
  be very good, very stable, fast, and the API was
  well thought out. However, it was just too
  expensive for us.
• Old technology not offering new functionality.
  High cost, in particular for new licenses.
• Daycart (at least at that time) did not take MOL
  query, not all query structures could be
  correctly presented as smiles/smarts.
• Two main reasons were the maintainance cost, and
  the accessibility. We had to suppress the raising
  system (software) cost, and at the same time we
  had to enlarge the number of users and client PCs
  from which we could use DB system.
• Cost, maintenance and risk

41
Migration Experience

• 5. What alternative platforms were
  considered/evaluated?
• Prior to selecting ChemAxon we looked at all the
  cartridges available at the time
• The Accord cartridge was also evaluated. Some
  others did not qualify for evaluation.
• None
• Accord (Accelrys), and ChemOffice (Cambridge
  Soft) were two major alternatives.
• Symyx/MDL Direct Oracle cartridge
• 6. Why did you choose ChemAxon technology?
  (advantages)
• Cost was a major factor, but also because we felt
  we could work with ChemAxon to develop the tools
  further as we wanted to use them. A very open
  approach. Another reason was that all the tools
  we needed were available from a single vendor,
  i.e. Oracle cartridge for searching, and
  sketching and viewing tools.
• Almost as good as Accord but with better impact
  on improvement and support.
• Marvin Sketch and JCart represent the molecules
  in MOL using exactly the same backend library.
  MOL is used instead of smiles/smarts. Much faster
  search. Price is good .
• We could keep the cost lowest by using ChemAxon,
  and more than that, the affinity for the web
  technology was favorable to our future vision of
  the cheminformatics system.
• The greatest advantage is the low cost and great
  support. We have always had MDL/Direct cartridge,
  but the greatest advantage is the low cost and
  stellar support speaks specifically to ChemAxon.

42
Migration Experience

• 7. What were the most problematic issues occurred
  during the migration? (negative impressions)
• Understanding the finer points of all the search
  functions / options i.e. precisely how things
  like aromaticity, stereochemistry, etc. are
  handled. We've also had to spend time considering
  how to restandardise structures and how to
  rewrite SQL. When doing a straight forward
  structure search (i.e. benchmarking), the JChem
  cartridge performs very well against other
  systems such as Daylight, however, if you want to
  incorporate joins between tables can considerably
  affect the query times even when using what we
  call ChemAxon SQL.
• Structure matching bugs in the cartridge and
  undocumented actions needed to be performed.
• JCart installation was not so smooth 3 years ago.
  Much better now. Most of the problem and issues
  are because some structures are interpreted
  different between the two software. Some are
  Daylight bugs and others are jchem bugs. JChem
  has fix all their share.
• There were little problem, what I remember is
  that the response was slower than expected when
  the chemical object was included in the page.
• Identifying all the integration points.

43
Migration Experience

• 8. How could you overcome in these difficulties?
  (resolutions)
• We spent a lot of time experimenting with the
  different functions/options so we completely
  understand what they do.
• The structure search bugs was overcome by
  rewriting the registration procedures,
  undocumented actions were overcome by hard work.
• Wait until major bugs in JChem are fixed. We live
  with about 0.01 of inconsistencies and work it
  out later.
• The needless chemical objects were replaced by
  pictures.
• Availability and quick turn around to patch any
• 9. Did you expect any other problem, that did not
  occur? (positive impressions)
• We though there may be problems running two
  different cartridges on the same table but this
  worked fine
• Not really. Most MDL features were available in
  JChem. This was one of the selection criteria,
  particularly important for chemical registration.
• No
• We expected that the transfer of the existing
  data might be problematic, and that the system
  change might be inconsistent with existing 'wet'
  workflow. That was why we organized 11 users as a
  system designing team, and I think the team
  worked well.
• Migration went very smooth

44
Migration Experience

• 10. What additional components were purchased
  together with the JChem Cartridge?
• Most of them!
• Descriptor calculations.
• None. User probably should consider plug-ins for
  calculating HBD, HBA, logp, psa, etc. We did not
  because we need to stick to CLOGP in order to be
  consistent with the rest of the company.
• Standardizer.
• Standardizer.
• 11. How much technical support did you need from
  ChemAxon for the migration?
• Initially quite a lot, though the products have
  been developed a lot since then. We haven't
  required much support for structure migration,
  but we've also migrated a load of SMIRKS and
  we've needed support for that mainly because of
  the way in which they were handled in the old
  system (non-standard).
• A few needed support cases where filed on the
  support forum and fairly quickly resolved.
• Lots, we had close communication with dev team
  during the migration.
• Our technical people sent e-mail several times to
  your support team.
• Little.

45
Migration Experience

• 12. Were/Are you satisfied with the ChemAxon
  support?
• Yes. Support has always been good.
• Yes very satisfied. The support has always been
  very fast and accurate.
• Yes.
• Yes.
• Yes.
• 13. Did the migration reach its original goals?
• So far, yes! The systems are up and running.
• Yes.
• Yes.
• Yes.
• Yes.

46
Migration Experience

• 14. Are you satisfied with the performance/functio
  ns of the ChemAxon powered system?
• The number of functions available and flexibility
  of the JChem tools is excellent, and allows us to
  develop very interesting and useful drug
  discovery software for our scientists.
• Yes.
• Yes.
• Yes.
• Yes.

47
Useful migration resources
ChemAxon's Marvin JChem (v 3.1.3) vs. MDL
ISIS/Draw ISIS/Host (v 4.0)Seong Jae Yu, David
Roush, Usha Ganesh, Young Moon, Henry Liu, FMC
Corp. http//www.chemaxon.com/conf/FMC_ChemAxon_JC
HEM_Cart_xnotes.ppt User Group Meeting
presentations http//www.chemaxon.com/UGM/ugm_lan
d.html
48
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

49
Cheshire Alternatives from ChemAxon

• What is Cheshire?
• Cheshire is a scripting language that enables
  you to write scripts to validate, modify, or
  gather information about chemical structures,
  such as molecules and reactions.
• What alternatives can ChemAxon offer?
• ChemAxons Java API (also available from .NET)
• Chemical Terms
• Standardizer

50
Java API for Cheminformatics from ChemAxon
ChemAxons class library consists of more than
1500 chemistry related classes tuned for
usability and high performance.
51
Chemical Terms
Chemical Terms offers more than a hundred popular
chemistry functions opening up the power of
cheminformatics for those scientists who focus on
quick results instead of the details of
programming and scripting. The integration of
Chemical Terms makes make chemistry applications
smarter and more customizable.
charge() and match(amine) or match(hydrazine)
52
Standardizer for Batch Conversion
Standardizer is a batch conversion utility
providing many useful and customizable functions
for the canonicalization of chemical structures
and restoration renovation chemical information
in structures from older databases.
53
Standardizer Actions
Transform
Clear Stereo
Aromatize
Set Absolute Stereo
Dearomatize
Remove Absolute Stereo
Add Explicit Hydrogens
Convert Wedge Interpretation
Remove Explicit Hydrogens
Convert Double Bonds
Clean2D
Alias to Group, Alias to Atom
Clean3D
Contract Group
Wedge Clean
Expand Group
Clear Isotopes
Ungroup
Remove Fragments
Expand Stoichiometry
Remove R-groups
Map Reaction
Tautomerize
Unmap
Neutralize
Mesomerize
54
Counting Groups Cheshire
Counting OSO groups in Cheshire
55
Counting Groups Java API
Counting any functional groups with ChemAxons
Java API
Counting OSO groups in Chemical Terms
56
Adding Explicit Hydrogens - Cheshire
Adding explicit hydrogens and cleaning the
molecule in Cheshire
57
Adding Explicit Hydrogens Java API
Adding explicit hydrogens and cleaning the
molecule with ChemAxons Java API
58
Adding Explicit Hydrogens Standardizer
Adding explicit hydrogens and cleaning the
molecule with Standardizer
The same in command line
59
Group Conversions Cheshire
Conversion of neutral form of nitro to the ionic
one in Cheshire
60
Group Conversions Java API
Conversion of neutral form of nitro to the ionic
one with ChemAxons Java API
61
Group Conversions Standardizer
Conversion of neutral form of nitro to the ionic
one in Standardizer
The same in command line
62
Structure Checker Framework
The new Structure Checker framework will provide
plenty of validation and correction functions to
detect and repair defective or unpreferred
structures.

• ValenceChecker
• AromaticityChecker
• OverlappingAtomsChecker
• OverlappingBondsChecker
• CrossedDoubleBondChecker
• WigglyDoubleBondChecker
• WedgeBondsChecker
• BondLengthChecker
• BondAngleChecker
• AliasChecker
• PseudoAtomChecker
• AbbreviatedGroupChecker
• MultiComponentChecker
• QueryChecker
• MoleculeChargeChecker
• RadicalChecker
• IsotopeChecker
• ExplicitHydrogenChecker
• StereoDoubleBondChecker

• ChiralFlagChecker
• CovalentSaltChecker
• FerroceneChecker
• CumulatedRingBondChecker
• UnbalancedReactionChecker
• MultistepReactionChecker
• AtomMapChecker
• MissingAtomMapChecker
• AtomMapStyleChecker
• RgroupQueryChecker
• MarkushChecker
• 3DCoordinateChecker
• MolfileChecker
• RxnfileChecker
• SmilesChecker
• SmartsChecker
• InchiChecker
• PeptideSequenceChecker
• CmlChecker

63
Summary

• ChemAxons Java API provides similar freedom and
  flexibility to Cheshire for programmers to
  develop chemistry functions for any tears like
  web clients, desktop applications, server systems
  and Oracle stored procedures.
• Java is a standard language with worlwide
  community, rich resources and lots of well
  educated developers. (The ChemAxon Java API is
  also accessible from .NET.)
• Chemical Terms provides more than a hundred high
  level, ready to use functions substituting dozens
  of lines of complex Cheshire code.
• Chemical Terms expressions can directly be used
  in database filters, virtual reactions,
  pharmacophore definitions or other
  cheminformatics applications.
• Standardizer is an easy to use batch tool and
  graphical interface for chemists to create
  conversion rules without writing a single line of
  code.
• The upcoming Structure Checker will provide and
  extensible set of quick problem detection
  functions that can be integrated in any
  applications and will be added to Marvin and
  Standardizer as well.

64
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

65
Instant JChem is

• An out of the box desktop application designed
  for biologists and chemists
• A modular platform for developing chemistry
  applications

66
Instant JChem lets users

• Create or connect to existing structure databases
• Easily manage relational data
• Import/export/merge/edit data
• Build forms for reporting
• Run combined structure data searches
• Perform structure based predictions
• Access sophisticated chemistry features
• Collaborate with other users

67
Feature comparison to ISIS/Base
68
IJC Architecture

• Built on modular platform
• Allows easy extension by ChemAxon, customers and
  3rd parties
• Strong enforcement of APIs
• API
• Allows extension
• IJC functionality is built upon these APIs

69
Current architecture
IJC Client
Database
Local DB
Remote DB
Oracle cartridge
70
IJC server architecture
Database
IJC Client
IJC Server
IJC
Services API
Oracle cartridge
IJC server due Q1 2009
71
Migration issues general
72
Migration issues migration of ISIS DBs
73
Hview vs. Data Tree standard tables
ISIS Hview HVIEW my_data TREE master DEVICE
oracle USERNAME scott PASSWORD tiger
TNAME master_table TREE detail DEVICE oracle
USERNAME scott PASSWORD tiger TNAME
detail_table LINK master (master_table_id) over
detail (master_table_id)
One-to-many relationship
master_table master_table_id col1 col2 col3
detail_table detail_table_id master_table_id cola
colb colc

74
Hview vs. Data Tree Mol Rxn tables
ISIS Hview HVIEW cpds_inv TREE compounds
DEVICE chemicaldb USERNAME CPD/CPD
PASSWORD TNAME compounds TREE inventory
DEVICE oracle USERNAME scott PASSWORD
tiger TNAME inventory LINK compounds
(molregno) over inventory (molregno)
lt RC tablesgt
inventory inventory_id molregno cola colb colc

75
Migration options
76
Migration local ISIS databases

• Analyse data hierarchy
• Export data as SDF/RDF
• Import into IJC
• Build forms
• Maybe possible to automate by writing COM
  application to read data from ISIS and write to
  Oracle database.

77
Migration ISIS/Host databases

• Analyse database tables and Hview
• Migrate RCG tables to JChem table(s)
• Connect IJC to the database
• Promote tables/columns/foreign keys into IJC
• Assemble IJC Data Tree
• Build forms
• May be possible for some automation.

78
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

79
JChem for Excel

• Microsoft Excel integrated solution for Marvin
  and JChem functionality
• Use Excels powerful features Functions,
  Sorting, Filtering, Charts
• Implemented in C .NET, and Visual Studio
• Proof that ChemAxon APIs can be used in a
  Java-less .NET environment
• Easy to install and deploy
• UNDER DEVELOPMENT

80
ISIS for Excel to JChem for Excel

• Import ISIS SARTables (January 2009)
• Workbook exported from ISIS for Excel
• Migration of standard ISIS Workbooks?

81
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

82
Custom Applications

• Java Applications
• Swing
• .NET Applications
• JNBridge Commercial Java - .NET Proxy
• Byte Code to IL (.NET binary) translation (IKMV)
• Open Source, very good performance
• No full GUI support at the moment, but coming
• JChem for Excel is built using IKVM
• Web Based Applications
• JSP, ASP.NET, AJAX
• SOAP

83
Custom Components

• Plans to release custom components
• Java Swing
• AJAX Examples
• .NET
• Visual Studio integrated
• Windows Forms (from JChem for Excel),WPF?
• ASP.NET
• ASP.NET AJAX, MVC

84
.NET Integration Enhancements

• Problem ChemAxon API uses Java Classes, not
  familiar to .NET developers
• Higher Level .NET wrappers, components
• Properties, Events
• Search results in DataSet, IDataReader
• LINQ, IEnumerable interfaces
• GUI Components DataGridView, Property Grids,
  Components for Search

85
Custom Application Migration and Development

• Resources and experience for migrating custom
  ISIS(Host - Base) based applications
• ISIS Forms to other applications
• Procedural Language (ISIS/PL)
• Consultation
• Help with custom application development on
  ChemAxon platform
• Both in-house (CXN) staff and partner companies
  are available
• Custom/prioritised improvements of ChemAxon
  products

86
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• ChemAxon for Developers (Resources)

87
Web Services

• Extends ChemAxon functionality to Web
  applications
• Enables interoperability from multiple
  programming languages with SOAP Protocol
• Allows migration of existing web applications to
  ChemAxon services
• Encourages creation new web applications

88
Service Modules

• Application Building Blocks
• DB Searching
• Substructure, Similarity, Exact, etc.
• Molecular Standardization
• Clustering and Diversity
• Chemically Intelligent Tools
• Shorthand Chemical Terms and Calculator Plugins
• Lipinski Rule of 5, pKa, logP, logD, etc.
• Molecular Format Conversion
• Image Generation

89
SOAP Protocol

• SOAP protocol used by most major web application
  languages
• Programming languages
• Java
• .Net (C, ASP.net)
• Scripting languages
• JavaScript
• Perl
• Python
• Etc.

90
AJAX Example
91
Migration of Existing Web Apps

• ChemAxon Web Services can be called from existing
  web services
• ChemAxon Web Services can directly replace
  specific functionality
• Migrate using Security Standards
• WS-Security, WS-Security Policy
• Integrate with existing authentication services
  (e.g. LDAP, Active Directory)

92
Creation of New Web Apps

• Standard WSDL files allow for automated client
  side code generation (Python, Perl, Java, C,
  etc.)
• AJAX provides asynchronous and desktop
  application performance
• Easily integrate with Marvin applets

93
Migration - Topics

• ChemAxon - Product Overview
• From Isis/Host and MDL Direct to JChem Cartridge
• Alternatives to Cheshire (Standardizer)
• From ISIS/Base to Instant JChem
• From ISIS for Excel To JChem for Excel
• Migrating Custom Applications
• ChemAxon Web Services
• Appendix ChemAxon for Developers (Resources)

94
API and Compatibility

• Java API (Marvin GUI included)
• Marvin Applets for web applications
• .NET API over JNBridge (Marvin GUI included)
• Native .NET solution under development (Marvin
  GUI included)
• API from SQL JChem Cartridge for Oracle
• SOAP interface (Python, C, .NET, ... over SOAP)
  under development
• AJAX interface under development (Marvin GUI
  included)
• Instant JChem highly configurable Java API
• Integration Pipeline Pilot, KNIME, Spotfire, ...

95
Java API

• Direct manipulation of structures
• Format conversions, nameltgtstructure, image
  generation
• Structure searching with/without DB access
• Standardization of structures
• Property calculations
• Reaction modelling (enumeration)
• Clustering
• Sketcher, 2D/3D viewers (Marvin family)
• Etc
• JChem API

96
Marvin Applets for Web Applications

• All relevant browsers (IE, FF, Safari, ...)
• Manipulation from HTML page (from JavaScript)
• Catching drawing events in JavaScript
• Can be used from .NET applications using the web
  browser control
• Marvin demo
• MarvinSketch Applet Examples
• MarvinView Applet Examples
• MarvinSpace Applet Examples

97
.NET API Over JNBridge

• Tight integration with .NET
• Full Java API is mirrored in .NET
• Marvin GUI components are also supported

98
Native .NET Solution

• Translating the non-GUI elements to Java binary
  to .NET binary (using IKVM)
• Building a thin .NET GUI for Marvin and other
  tools over the core.
• Advantages
• Pure .NET solution, Java is not needed to be
  installed
• No license issue
• No performance overhead of proxying
• under development

99
JChem Cartridge for Oracle

• API from Oracle SQL
• All features needed for structure handling and
  searching
• Fast searching, insertion, and indexing
• Special features
• Standardization of structures is tied with
  structure tables
• Property calculations
• Format conversions, nameltgtstructure, image
  generation
• Reaction and Markush based structure enumeration
• Markush libraries in structure tables (coming
  soon)

100
SOAP Interface

• Web services interface to most functionalities
• Bridges to Python, C, Perl, .NET, Java using WSDL
• Enables both remote and local access to ChemAxon
  functionalities
• under development

101
AJAX GUI

• AJAX components for web applications
• Customization using CSS and XSL
• Accesses SOAP interface
• Structure searching, database handling example
• Fast and rich GUI
• Floating windows
• Scrolling through large database without paging
• Marvin Applets are integrated
• under development

102
Instant JChem for Developers

• Sharable forms, queries, lists
• URL-s to sharable items - Demos
• Instant JChem API

103
Integrations

• Several software vendors integrated ChemAxon
  components
• Pipeline Pilot
• KNIME (by Infocom)
• Spotfire
• Aureus
• Integrity (Thomson)
• Others (Agilent, Tripos, Symyx, Deltasoft, GVK,
  Wiley, Genedata, Contur, Inforsense, Kinematik,
  Houghton Mifflin, Kelaroo, Patcore, Cengage,
  Prentice Hall, Crossfire Beilstein, etc)

104
Visit other technical presentations
ChemAxon Overview http//www.chemaxon.com/conf/Che
mAxon_Overview.ppt MarvinSketch/View http//www.ch
emaxon.com/MarvinSketch_View.ppt MarvinSpace http
//www.chemaxon.com/MarvinSpace.ppt Calculator
Plugins http//www.chemaxon.com/Calculator_Plu
gins.ppt Structural Search http//www.chemaxon.co
m/Structural_Search.ppt JChem Base http//www.che
maxon.com/JChem_Base.ppt Instant JChem
http//www.chemaxon.com/conf/Instant_JChem.ppt J
Chem Cartridge http//www.chemaxon.com/JChem_Cartr
idge.ppt Standardizer http//www.chemaxon.com/Sta
ndardizer.ppt Screen http//www.chemaxon.com/Scr
een.ppt JKlustor http//www.chemaxon.com/JKlustor
.ppt Fragmenter http//www.chemaxon.com/Fragmente
r.ppt Reactor http//www.chemaxon.com/Reactor.pp
t
105
Find out more

• Product descriptions links
• www.chemaxon.com/products.html
• Forum
• www.chemaxon.com/forum
• Presentations and posters
• www.chemaxon.com/conf
• Download
• www.jchem.com/licensefrset.html

106

• Thank you for your attention!