(ATS4-PLAT04) Chemistry Data Model Enhancements inPipeline Pilot 9.0: what are they and how will they impactyour users    ...
The information on the roadmap and future software development efforts areintended to outline general product direction an...
Pipeline Pilot 9.0 – New Capabilities• Enhanced representation    – What you see is what you have• New representations    ...
Pipeline Pilot 9.0 – New Capabilities•   Pipeline Pilot 9.0 (2013) will support all chemical representations supported by ...
Chemical Representations – New in 9.0•   Single/double/triple bonds supported in NONS•   Coordination/Dative bond•   Hapti...
Depiction• Rendering between Accelrys Draw and Pipeline Pilot  9.0 now consistent                                 Draw• Pi...
Abbreviated groups render correctly•   Abbreviated groups are frequently used to simplify structures                      ...
Rgroup/Markush is functional•   Markush/Rgroup depiction is complete in    Pipeline Pilot rendering                       ...
Nonspecific representations are rendered                                                                      Pipeline•   ...
Biologics•    Growing importance•    Representation exposed in Pipeline Pilot 8.5•    Completed in 9.0       – Much more f...
Polymers, Mixtures, and Formulations New in 9.0• Representation and search new in 9.0• Mix it up
Example: Antibody-Drug Conjugates – New in 9.0•   Accelrys Direct and Accelrys Draw understand Antibody-Drug Conjugates
Example: Antibody-Drug Conjugates•   Pipeline Pilot 9 understands Antibody-Drug Conjugates (ADC)     – And with variable l...
What does this mean to my scientists? (1)• Higher quality reports    – Supports perception of quality research• Enhanced d...
Mapping: Non Specific Structures - New• Enhanced mapping – New in 9.0 e.g. Imipramine Metabolites
Mapping: Homology group screening•   Screen MDDR data set     –   129,237 structures screened in ~30s     –   No pre-proce...
What does this mean to my scientists? (2)• New mapping capabilities   – No change to existing protocols   – Enhancements t...
Data Model Changes from PP 8.x  PP9•   Changes to stereochemical and aromaticity perception will drive changes in the    ...
Compatibility: Pipeline Pilot and Accelrys Direct•   Pipeline Pilot 9.0 (2012) and Accelrys Direct 9.0 (2013)     –   Will...
Observed Differences in Calculated Values•         Table shows the number of structures in the datasets that had different...
Harmonization delivers• Single chemistry foundation with single data model implemented in  a single code stream    – Adopt...
Summary• Chemistry Harmonization project:    –   PPChem 9.0 inherits many new chemical representations    –   Existing rep...
Chemistry Data ModelChanges to Chemical PerceptionDetails
Valence and Implicit Hydrogens•   Charged non-metals are now treated as their “isoelectronic” equivalent:     –   B- ~ C ~...
Rings•   Ring perception has been improved. Previously, the SSSR ring perception algorithm was used, which is    not uniqu...
Aromaticity Perception•  The isoelectronic equivalence enhancement described in Valence and Implicit Hydrogens improves th...
Stereochemical Perception•  The isoelectronic equivalence enhancement described in Valence and Implicit Hydrogens improves...
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(ATS4-PLAT04) Chemistry Data Model Enhancements in Pipeline Pilot 9.0: what are they and how will they impact your users

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Pipeline Pilot Chemistry is inheriting many new chemical representations from the Accelrys Direct data model. These include the support of the Self Contained Sequence Representation (SCSR) biologics, enhanced Markush structure representations, Markush homology groups and Non Specific Structures (NONS). PPChem’s current support for Sgroups, and in particular polymers, mixtures, and formulations is significantly enhanced.

Depiction is also being upgraded to support these new features and enhancements, and the general aesthetics of depiction is improved.

The stereochemical perception, and ring perception capabilities of the Direct data model are superior to those currently offered in PPChem and are being incorporated. Changes to stereochemistry and ring perception may impact your calculators and models. We will report our findings on the magnitude of the changes.

A major benefit of these changes is that Direct and PPChem will use the same data model. This means that searches carried out in Direct or in PPChem will return identical results and both products will deliver identical structural perceptions.

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(ATS4-PLAT04) Chemistry Data Model Enhancements in Pipeline Pilot 9.0: what are they and how will they impact your users

  1. 1. (ATS4-PLAT04) Chemistry Data Model Enhancements inPipeline Pilot 9.0: what are they and how will they impactyour users Keith T Taylor PhD Advisory Product Manager, Chemistry Foundation keith.taylor@accelrys.com
  2. 2. The information on the roadmap and future software development efforts areintended to outline general product direction and should not be relied on in makinga purchasing decision.
  3. 3. Pipeline Pilot 9.0 – New Capabilities• Enhanced representation – What you see is what you have• New representations – New mapping options – Streamlined mapping• Consistency between Pipeline Pilot Chemistry, Accelrys Direct, and Accelrys Draw• Changes to perception mean that models, and calculators must be relearned and re-baselined – Significant effect from new ring perception option – Stereochemistry and aromaticity have smaller, but important effect
  4. 4. Pipeline Pilot 9.0 – New Capabilities• Pipeline Pilot 9.0 (2013) will support all chemical representations supported by Direct and Draw – Generics – Biologics – Polymers and Mixtures – Variable attachments – Homology Groups – Haptic Structures – New bond types• Depiction of all chemical objects supported by Accelrys Direct and Accelrys Draw – Look and feel that matches those of Accelrys Draw• Mappers upgraded to support new representations• Calculators upgraded to interpret the new representations appropriately• Enhanced perceptions of stereochemistry. aromaticity, and rings
  5. 5. Chemical Representations – New in 9.0• Single/double/triple bonds supported in NONS• Coordination/Dative bond• Haptic bonds• Markush Homology Groups• Hydrogen bonds
  6. 6. Depiction• Rendering between Accelrys Draw and Pipeline Pilot 9.0 now consistent Draw• Pipeline Pilot now supports: – PNG – JPEG – GIF – SVG – EMF – Linux and Windows! Pipeline• SVG and EMF generation fast Pilot – ~ 10,000 structures per second
  7. 7. Abbreviated groups render correctly• Abbreviated groups are frequently used to simplify structures Draw• Attachment points are now correct – The Pipeline Pilot 8.x depictions are incorrect on the left of the phenyl group – The labels depicted imply different chemical entities • Visual corruption • Nitrile (CN) and isonitrile (NC) are chemically different • NCS and SCN are also different entities Pipeline Pilot• Rich text markup renders correctly• Whitespace around labels is consistent – Affects perceived bond length
  8. 8. Rgroup/Markush is functional• Markush/Rgroup depiction is complete in Pipeline Pilot rendering Draw• Now renders – Rgroups definitions (e.g. R1 …) – Rgroup logic (R1 = 1; R2 >= 0) – Indication of direction for fragments with multiple attachment points (e.g. “ on R2) Pipeline Pilot
  9. 9. Nonspecific representations are rendered Pipeline• Nonspecific (NONS) representation are equivalent with Pilot Direct 8.0 and Draw 4.1 – Pipeline Pilot version does not lose information• Examples from mass spectrometry and industrial chemicals Draw Draw Pipeline Pilot
  10. 10. Biologics• Growing importance• Representation exposed in Pipeline Pilot 8.5• Completed in 9.0 – Much more functional and sophisticated DrawPipelinePilot
  11. 11. Polymers, Mixtures, and Formulations New in 9.0• Representation and search new in 9.0• Mix it up
  12. 12. Example: Antibody-Drug Conjugates – New in 9.0• Accelrys Direct and Accelrys Draw understand Antibody-Drug Conjugates
  13. 13. Example: Antibody-Drug Conjugates• Pipeline Pilot 9 understands Antibody-Drug Conjugates (ADC) – And with variable loading• Harmonization facilitates support of all of Accelrys’ chemical representation in applications – Antibody-drug conjugates, polymers, formulation, mixtures, and metabolites• Benefits of harmonized chemical representation are: – Implement once – Expose everywhere – Consistent
  14. 14. What does this mean to my scientists? (1)• Higher quality reports – Supports perception of quality research• Enhanced depiction of biologics and Markush generics – Will look different and minor adjustments to depiction protocols may be needed• New chemical representations – No change to existing protocols – New opportunities open up
  15. 15. Mapping: Non Specific Structures - New• Enhanced mapping – New in 9.0 e.g. Imipramine Metabolites
  16. 16. Mapping: Homology group screening• Screen MDDR data set – 129,237 structures screened in ~30s – No pre-processing Hits = 470 Hits = 108 Hits = 45 Hits = 16 Hits = 10
  17. 17. What does this mean to my scientists? (2)• New mapping capabilities – No change to existing protocols – Enhancements to existing protocols – more efficient code – New screening opportunities – screen by homology
  18. 18. Data Model Changes from PP 8.x  PP9• Changes to stereochemical and aromaticity perception will drive changes in the behavior of: – Learned models – Calculators – Structure Matchers• Will need to relearned and re-baselined• Change is discontinuous• There will be no legacy mode – Because this will cause incompatibilities and drive confusion
  19. 19. Compatibility: Pipeline Pilot and Accelrys Direct• Pipeline Pilot 9.0 (2012) and Accelrys Direct 9.0 (2013) – Will be 100% compatible• Pipeline Pilot 9.0 and Accelrys Direct 8.0 – Only difference is aromaticity perception edge-cases – Direct 8.0 will use its current aromaticity perception • Template based – Will differ from that in Pipeline Pilot 9.0 • Hückel (4n+2) rule based – Minor differences will be observed
  20. 20. Observed Differences in Calculated Values• Table shows the number of structures in the datasets that had different values in 9.0 compared with 8.5 Number of Canonical Number of Number of Number of Dataset AlogP ECFP4 Structures SMILES Rings Aromatic Rings Stereo Atoms ACD 239,996 251 105 2,455 65 0 214 Asinex 137,799 26 24 1,070 22 0 43 Maybridge 51,058 2 0 438 0 0 1 MDDR 2010 201,748 62 24 3,271 29 4 46 WDI 53,517 37 14 612 10 0 42• Difference generally very small• Ring perception leads to more prominent differences especially in drug-like datasets
  21. 21. Harmonization delivers• Single chemistry foundation with single data model implemented in a single code stream – Adopted by Tools and Platform • Direct , Pipeline Pilot and Accelrys Enterprise Platform – Application Stack inherits all of the chemistry capabilities• Simplifies development and application environment• Enhances our ability to deliver to you new functionality more quickly across the products
  22. 22. Summary• Chemistry Harmonization project: – PPChem 9.0 inherits many new chemical representations – Existing representations enhanced – Aromaticity, Stereochemistry and Ring perceptions enhanced – Significant improvement to depiction aesthetics – PPChem 9.0 and Direct 8.0 share representations(1)• Pipeline Pilot 9 and Direct 9 deliver the same results• What Next – Get early access by joining the beta2 program – Get feedback from your chemists – What opportunities do the new features open up?• Related Tech Summit Sessions (Current or previous)]
  23. 23. Chemistry Data ModelChanges to Chemical PerceptionDetails
  24. 24. Valence and Implicit Hydrogens• Charged non-metals are now treated as their “isoelectronic” equivalent: – B- ~ C ~ N+ ~ O+2 ~ F+3 – Si- ~ P ~ S+ ~ Cl+2• The bad valence filter has been improved and now catches more bad anions.• Metal anions no longer have implicit hydrogens – Aluminum anions are an exception (for support of aluminum hydride anion)• Nitrogen (V) is still allowed as a drawing alternative for nitro- and diazo- groups, amine oxides, and related substructures. However, the application is now less likely to perceive uncharged quaternary nitrogens as implicit hydrogens.• Atoms with illegal valence are now better distinguished from atoms with maximum valence in ECFP fingerprint bits. For example, the Oxygen in N=O and N#O is now typed differently. This can affect the Canonical SMILES atom order for structures containing atoms with illegal valence.• The changes in valence result in changes to ECFP fingerprint bits and Canonical SMILES.
  25. 25. Rings• Ring perception has been improved. Previously, the SSSR ring perception algorithm was used, which is not unique and often misses rings in complex non-planar assemblies, when they were atom-order and bond-order dependent. The unique “K-rings” perception algorithm is now used, which is the union of all possible SSSR sets. These changes result in changes to Canonical SMILES and improvement to aromaticity perception.• Examples• Now perceived as 3 rings:• Now perceived as 4 rings:• Now perceived as 6 rings:
  26. 26. Aromaticity Perception• The isoelectronic equivalence enhancement described in Valence and Implicit Hydrogens improves the perception of ring systems containing charged non-metals. Improved detection of bad valence for anions also contributes to improved perception of aromaticity.• The atoms that can contribute a lone pair to an aromatic ring are extended from (N,O,P,S) to include As, Se, and Te.• These changes result in changes to ECFP fingerprint bits and Canonical SMILES.Examples• Now perceived as aromatic:• No longer perceived as aromatic:
  27. 27. Stereochemical Perception• The isoelectronic equivalence enhancement described in Valence and Implicit Hydrogens improves the perception of stereogenic centers that include charged non-metals.• The symmetric equivalence of O-/OH/=O groups attached to P and S atoms has been extended to include As, Se, and Te centers.• Stereo validation logic of reader code is synchronized with perception code. This allows for more consistent application of rules prohibiting S(IV) centers, P(V) centers, symmetric equivalence of O- /OH/=O, etc.• “Double-symmetric” ring atom perception is improved Several symmetric spiro cases are now correctly not marked as pseudo-stereo.Examples• Now perceived as stereo:•• More consistently perceived as not stereo:•

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