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Computational Chemical Biology
Group coordinators: Irene Kouskoumvekaki, Olivier Taboureau
Members: Alireza Kashani, Kasper Jensen, Louis Wich, Sonny Kim Kjærulff, Tudor Oprea, Ulrik Plesner Jacobsen
Guest members: Damian Rafal Plichta, Soeren Skovstrup Ethelberg
Catalog of previous student projects.
About the group
Common human diseases result from the interplay of many genes and environmental
factors. Furthermore, a drug rarely acts only on one target but follows a
similarly complex interaction with proteins. Therefore, an integrative chemical
biology approach is needed to unravel the genetic background of diseases and to
provide the best possible medicinal treatment.
The Computational Chemical Biology group at CBS has evolved from the former
group of Chemoinformatics, with interest in exploring via computational methods
the interplay between small molecules and biological systems.
Current areas of interest include
- Chemogenomics mapping of natural compounds.
- Associating drugs and drug candidates to clinical outcomes via therapeutic targets and protein-protein interaction networks.
- Predicting adverse effects of drugs via tissue-specific gene expression data.
- Predicting the activity profiles of new psychoactive drug candidates by building informative drug-target interaction networks.
The overall aim of the research focus of CCB is to elucidate the biological profile of small molecules regarding their targets, off-targets, phenotypic outcome and side-effects via an in-depth understanding of the biological networks that lead to disease and the perturbations on them that can be caused by small molecules.
Data collection
- ~ 55.000 natural products
- ~ 700.000 drugs and druglike compounds with protein targets and/or disease annotation
- ~ 20 million molecules
Expertise: molecular modeling, machine learning methods (QSAR, NN, SVM,...), chemogenomics and chemical-biological networks.
Fields
- Transporters, GPCR
- Nuclear receptors
- Metabolism and cytochrome P450
- Toxicity
- Antimicrobial Peptides
Online services
pHSol: Predictor of pH-dependent aqueous solubility of druglike small molecules
ChemProt: Resource of annotated and predicted chemical-protein interactions
hERG: Predictor of potential hERG channel inhibitors
Education
The group organizes and is responsible for the CBS course "Chemoinformatics in Drug Discovery" (masters level) and is thus leading the way in providing education in this field. If you are interested in learning more about the group please contact Olivier Taboureau or Irene Kouskoumvekaki.
Selected Publications:
- Pharmacophore-driven identification of PPARgamma agonists from natural sources. Petersen RK, Christensen KB, Assimopoulou AN, Fretté X, Papageorgiou VP, Kristiansen K, Kouskoumvekaki I, JCAMD, 2010
- The interplay of descriptor-based computational analysis with pharmacophore modeling builds the basis for a novel classification scheme for feruloyl esterases. Udatha DB, Kouskoumvekaki I, Olsson L, Panagiotou G, Biotechnology Adv, 2010
- Navigating the human metabolome for biomarker identification and design of pharmaceutical molecules. Kouskoumvekaki I, Panagiotou G, Journal of Biomedicine and Biotechnology, 2010
- Chemoinformatics-assisted development of new anti-biofilm compounds. Dürig A, Kouskoumvekaki I, Vejborg RM, Klemm P, Appl Microbiol Biotechnol, 2010
- ChemProt: a disease chemical biology database. Taboureau O, Nielsen SK, Audouze K, Weinhold N, Edsgärd D, Roque FS, Kouskoumvekaki I, Bora A, Curpan R, Jensen TS, Brunak S, Oprea TI, Nucleic Acids Research, 2010
- Mutational mapping and modeling of the binding site for (S)-citalopram in
the human serotonin transporter. Andersen J, Olsen L, Hansen KB, Taboureau O,
Jorgensen FS, Jorgensen AM, Bang-Andersen B, Egeberg J, Strømgaard K, Kristensen
AS, J. Biol. Chem. [Epub ahead of print], 2009
- Country-specific chemical signatures of persistent environmental compounds
in breast milk. Krysiak-Baltyn K, Toppari J, Skakkebæk NE, Jensen TS, Virtanen
HE, Schramm KW, Shen H, Vartiainen T, Kiviranta H, , Taboureau O, Brunak S, Main
KM, Int. J. Androl.,[Epub ahead of print], 2009
- Location of the antidepressant binding site in the serotonin transporter: Importance of SER438 in recognition of citalopram and tricyclic
antidepressants. Andersen J, Taboureau O, Hansen KB, Olsen L, Egeberg J, Strømgaard K, Kristensen AS, J. Biol. Chem. 284(15), 10276-10284, 2009
- Classification of cytochrome P450 1A2 inhibitors and non inhibitors by machine learning techniques and binary QSAR. Vasanthanathan
P,Taboureau O, Oostenbrink C, Vermeulen N, Olsen L, Jørgensen FS. Drug. Metab. Disp. 37(3), 658-664, 2009
- Virtual screening and prediction of site of metabolism for cytochrome P450 1A2 ligands. Vasanthanathan P, Hritz J, Taboureau O, Olsen L,
Jørgensen FS, Vermeulen N, Oostenbrink C, J. Chem. Inf. Model. 49(1), 43-52, 2009
- Prediction of pH-dependent solubility of Histone Deacetylase (HDAC)inhibitors. Kouskoumvekaki I, Hansen NH, Bjørkling F, Vadlamudi SM and Jónsdóttir SÓ, SAR and QSAR in Environmental Research, 19, 167-177, 2008
- A hERG Classification Model based on a Combination of Support Vector Machine Method and GRIND Descriptors. Li Q, Jørgensen FS, Oprea T, Brunak S and Taboureau O, Molecular Pharmaceutics, 5, 117-127, 2008
- Identification of biomarkers for genotyping Aspergilli using non-linear methods for clustering and classification. Kouskoumvekaki I, Yang Z, Jónsdóttir Só, Olsson L, Panagiotou G, BMC Bioinformatics, 9:59, 2008
- Kemoinformatik: Lær computeren at finde nye lægemidler. Kouskoumvekaki I, Hansen NT, Jónsdóttir Só, Dansk Kemi, 88, 23-25, 2007 (Also printed in Biozoom, 10, 19-23, 2007.)
- Monitoring novel metabolic pathways using metabolomics and machine learning; induction of the phosphoketolase pathway in Aspergillus nidulans cultivations Panagiotou G, Kouskoumvekaki I, Jónsdóttir SÓ and Olsson L, Metabolomics, 3, 503-516, 2007
- Prediction of pH-Dependent Aqueous Solubility of Druglike Molecules. Hansen NT, Kouskoumvekaki I, Jørgensen FS, Brunak S and Jónsdóttir SÓ, J. Chem. Inf. Model., 46, 2601-9, 2006
Full length list of CBS publications
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