ICCS 2022 talk on Improving Torsion Library Patterns with SMARTScompare

1. Patrick Penner
13 / 06 / 2022 1
MIN FACULTY
Center for BIOINFORMATICS
Improving Torsion Library Patterns
with SMARTScompare
Patrick Penner

2. Patrick Penner
13 / 06 / 2022 2
MIN FACULTY
Center for BIOINFORMATICS
Classifying Torsions
2ANS

3. Patrick Penner
13 / 06 / 2022 3
MIN FACULTY
Center for BIOINFORMATICS
Classifying Torsions
2ANS

4. Patrick Penner
13 / 06 / 2022 4
MIN FACULTY
Center for BIOINFORMATICS
Torsion Library
Penner et al. (2022). J. Chem. Inf. Model.
Guba et al. (2016). J. Chem. Inf. Model.
Schärfer et al. (2013). J. Med. Chem.

5. Patrick Penner
13 / 06 / 2022 5
MIN FACULTY
Center for BIOINFORMATICS
Matching

6. Patrick Penner
13 / 06 / 2022 6
MIN FACULTY
Center for BIOINFORMATICS
Matching
Cambridge Structural Database (CSD) Protein Data Bank (PDB)

7. Patrick Penner
13 / 06 / 2022 7
MIN FACULTY
Center for BIOINFORMATICS
Matching
[cH1:1][c:2]([cH0])!@[NX3:3][a:4]

8. Patrick Penner
13 / 06 / 2022 8
MIN FACULTY
Center for BIOINFORMATICS
SMARTScompare Schmidt et al (2019). J. Chem. Inf. Model.

9. Patrick Penner
13 / 06 / 2022 9
MIN FACULTY
Center for BIOINFORMATICS
Benzamidine Example

10. Patrick Penner
13 / 06 / 2022 10
MIN FACULTY
Center for BIOINFORMATICS
Benzamidine Example
[c:2][C:3](=N)(-N) [cH0:1][c:2]([cH0])!@[C:3](=[N:4])(-N)
Subclass Pattern Pattern with Incomplete Amidine

11. Patrick Penner
13 / 06 / 2022 11
MIN FACULTY
Center for BIOINFORMATICS
Benzamidine Example

12. Patrick Penner
13 / 06 / 2022 12
MIN FACULTY
Center for BIOINFORMATICS
Sorting Example
[*:1]~[NX2:2]!@[OX2:3]~[*:4]
[*:1]~[nX3:2]!@[OX2:3]~[*:4]
[*:1]~[N,n:2]!@[S:3]~[*:4]
[*:1]~[NX2:2]!@[SX4:3]~[*:4]
[*:1]~[NX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[SX2:3]~[*:4]
[*:1]~[N,n:2]!@[P:3]~[*:4]
[*:1]~[OX2:2]!@[SX4:3]~[*:4]
[*:1]~[OX2:2]!@[SX3:3]~[*:4]

13. Patrick Penner
13 / 06 / 2022 13
MIN FACULTY
Center for BIOINFORMATICS
Sorting Example
[*:1]~[NX2:2]!@[OX2:3]~[*:4]
[*:1]~[nX3:2]!@[OX2:3]~[*:4]
[*:1]~[N,n:2]!@[S:3]~[*:4]
[*:1]~[NX2:2]!@[SX4:3]~[*:4]
[*:1]~[NX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[SX2:3]~[*:4]
[*:1]~[N,n:2]!@[P:3]~[*:4]
[*:1]~[OX2:2]!@[SX4:3]~[*:4]
[*:1]~[OX2:2]!@[SX3:3]~[*:4]

14. Patrick Penner
13 / 06 / 2022 14
MIN FACULTY
Center for BIOINFORMATICS
Sorting Example
[*:1]~[NX2:2]!@[SX2:3]~[*:4]
[*:1]~[NX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[SX4:3]~[*:4]

15. Patrick Penner
13 / 06 / 2022 15
MIN FACULTY
Center for BIOINFORMATICS
Sorting Example
[*:1]~[NX2:2]!@[OX2:3]~[*:4]
[*:1]~[nX3:2]!@[OX2:3]~[*:4]
[*:1]~[N,n:2]!@[S:3]~[*:4]
[*:1]~[NX2:2]!@[SX4:3]~[*:4]
[*:1]~[NX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[SX2:3]~[*:4]
[*:1]~[N,n:2]!@[P:3]~[*:4]
[*:1]~[OX2:2]!@[SX4:3]~[*:4]
[*:1]~[OX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[OX2:3]~[*:4]
[*:1]~[nX3:2]!@[OX2:3]~[*:4]
[*:1]~[NX2:2]!@[SX4:3]~[*:4]
[*:1]~[NX2:2]!@[SX3:3]~[*:4]
[*:1]~[NX2:2]!@[SX2:3]~[*:4]
[*:1]~[N,n:2]!@[S:3]~[*:4]
[*:1]~[N,n:2]!@[P:3]~[*:4]
[*:1]~[OX2:2]!@[SX4:3]~[*:4]
[*:1]~[OX2:2]!@[SX3:3]~[*:4]
Pattern Matches Before Matches After
[*:1]~[N,n:2]!@[S:3]~[*:4] 2253 983
[*:1]~[NX2:2]!@[SX4:3]~[*:4] 0 1004
[*:1]~[NX2:2]!@[SX3:3]~[*:4] 0 135
[*:1]~[NX2:2]!@[SX2:3]~[*:4] 0 131
Sort

16. Patrick Penner
13 / 06 / 2022 16
MIN FACULTY
Center for BIOINFORMATICS
Torsion Tooling

17. Patrick Penner
13 / 06 / 2022 17
MIN FACULTY
Center for BIOINFORMATICS
Torsion Tooling (https://torsions.zbh.uni-hamburg.de)

18. Patrick Penner
13 / 06 / 2022 18
MIN FACULTY
Center for BIOINFORMATICS
Thank you
for your attention
Research Group for
Computational
Molecular Design:
Patrick Penner,
Matthias Rarey,
Roche:
Wolfgang Guba
Agnes Meyder
Martin Stahl
BioSolveIT:
Robert Schmidt

19. Patrick Penner
13 / 06 / 2022 19
MIN FACULTY
Center for BIOINFORMATICS
Additional Reading and Software Availability
TorsionAnalyzer Server:
https://torsions.zbh.uni-hamburg.de
NAOMI ChemBio Suite:
https://uhh.de/naomi
SMARTS Pattern Analyzer Server
https://smarts.plus
Modeling Support Server:
https://proteins.plus
Github:
https://github.com/rareylab

20. Patrick Penner
13 / 06 / 2022 20
MIN FACULTY
Center for BIOINFORMATICS
1. C. Schärfer, T. Schulz-Gasch, H.-C. Ehrlich, W. Guba, M. Rarey, and M. Stahl, “Torsion Angle
Preferences in Druglike Chemical Space: A Comprehensive Guide,” Journal of Medicinal
Chemistry, vol. 56, no. 5, pp. 2016–2028, 2013, doi: https://doi.org/10.1021/jm3016816.
2. W. Guba, A. Meyder, M. Rarey, and J. Hert, “Torsion Library Reloaded: A New Version of
Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules,” Journal of
Chemical Information and Modeling, vol. 56, no. 1, pp. 1–5, 2016, doi:
https://doi.org/10.1021/acs.jcim.5b00522.
3. P. Penner, W. Guba, R. Schmidt, A. Meyder, M. Stahl, and M. Rarey, “The Torsion Library:
Semiautomated Improvement of Torsion Rules with SMARTScompare,” Journal of Chemical
Information and Modeling, 2022-03, doi: https://doi.org/10.1021/acs.jcim.2c00043.
4. R. Schmidt, E. S. R. Ehmki, F. Ohm, H.-C. Ehrlich, A. Mashychev, and M. Rarey, “Comparing
Molecular Patterns Using the Example of SMARTS: Theory and Algorithms,” Journal of
Chemical Information and Modeling, vol. 59, no. 6, pp. 2560–2571, 2019, doi:
https://doi.org/10.1021/acs.jcim.9b00250.
References