representation of chemical data in qsar and crystallography

Representation of chemical data in QSAR and crystallography

–Egon Willighagen, Lunteren 2005

Computer representation of molecular structures

Representation of chemical datain QSAR and crystallography

Egon Willighagen, Lunteren 2005

•Connection Table

•Dietz Representation

•Physical Properties•Molecular Invariants

•Schrödinger Equation

•Spectra (NMR, IR, ...)

Computer representations of molecular structures



•Connection Table

•Dietz Representation

•Physical Properties•Molecular Invariants

•Schrödinger Equation

•Spectra (NMR, IR, ...)

Representing relations between descriptors

•• Descriptor ontology: explicit definition of descriptor

types and descriptor properties•••••

•C.Steinbeck, C.Hoppe, S.Kuhn, M.Floris, R.Guha, E.L.Willighagen, Recent Developments of the Chemistry Development Kit (CDK) - An Open-Source Java Library for Chemo- and Bioinformatics, Current Pharmaceutical Design, accepted



Representation does make a difference

• Use of NMR spectra in Quantitative Structure Activity Relationship (QSAR) modeling

• Three representations: simulated 1H NMR, 13C NMR spectra and theoretical descriptors

• Three data sets:– water solubility of 431 compounds (WS)– boiling points of 277 compounds (BP)– LogP values of 154 compounds (LogP)–



•E.L.Willighagen, H.M.G.W.Denissen, R.Wehrens, L.M.C.Buydens, On the use of 1H and 13C NMR spectra as QSAR descriptors, submitted

How the experiment is performed...

• Partial Least Squares

– 220 NMR bins– 220 randomly selected theoretical descriptors (Dragon)–– five random divisions in training and test sets–– number of latent variables chosen with leave-one-out cross

validation



Number of latent variables



1H and 13C NMR versus Dragon Descriptors



Prediction Errors



Model interpretation?



What can we conclude?

• Representation has a large effect

• 1H NMR models have no predictive power

• 13C NMR models have some predictive power ... but no advantages



Finding a representation for crystal structures



Electronic Radial Distribution Function (ReDF)

•• Describes patterns in atom interactions in and around the

unit cell



• Å

•E.L.Willighagen, R.Wehrens, P.Verwer, R.de Gelder, L.M.C.Buydens, A Method for the Computational Comparison of Crystal Structures, Acta.Cryst., 2005, B61, 29-36

Quantifying Similarities



Quantifying Similarities



ReDF 1

ReDF 2

Weighted

Cross

Correlation

Similarity [0,1]

Cephalosporin crystal structures



Polymorph Prediction

• Polymorphs: different crystal structures for the same molecular compound

• Polymorph Prediction: computational method to predict the polymorphs given a molecular structure



Polymorphic estrone crystal structures

• Better trend in similarity going from identical to different structures :

ReDF + WCC Cerius2



Conclusions

• It is important to pick a proper representation

• 1H and 13C NMR spectra are not good representations for QSAR models

• A new crystal structure descriptor for gives chemically better interpretable similarities



Acknowledgments

● Ron Wehrens, Lutgarde Buydens (supervisors)

● René de Gelder, Paul Verwer (crystal structures)

● Harm Denissen (QSAR)

● Peter Murray-Rust (Cambridge University, UK) Christoph Steinbeck (Cologne University, DE)

● NWO (for financial support)



representation of chemical data in qsar and crystallography

Health & Medicine

crystallography representation

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qsar descriptors

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