TY  - JOUR
A1  - Kaltdorf, Martin
A1  - Srivastava, Mugdha
A1  - Gupta, Shishir K.
A1  - Liang, Chunguang
A1  - Binder, Jasmin
A1  - Dietl, Anna-Maria
A1  - Meir, Zohar
A1  - Haas, Hubertus
A1  - Osherov, Nir
A1  - Krappmann, Sven
A1  - Dandekar, Thomas
T1  - Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach
JF  - Frontiers in Molecular Bioscience
N2  - New antimycotic drugs are challenging to find, as potential target proteins may have close human orthologs. We here focus on identifying metabolic targets that are critical for fungal growth and have minimal similarity to targets among human proteins. We compare and combine here: (I) direct metabolic network modeling using elementary mode analysis and flux estimates approximations using expression data, (II) targeting metabolic genes by transcriptome analysis of condition-specific highly expressed enzymes, and (III) analysis of enzyme structure, enzyme interconnectedness (“hubs”), and identification of pathogen-specific enzymes using orthology relations. We have identified 64 targets including metabolic enzymes involved in vitamin synthesis, lipid, and amino acid biosynthesis including 18 targets validated from the literature, two validated and five currently examined in own genetic experiments, and 38 further promising novel target proteins which are non-orthologous to human proteins, involved in metabolism and are highly ranked drug targets from these pipelines.
KW  - metabolism
KW  - targets
KW  - antimycotics
KW  - modeling
KW  - structure
KW  - interaction
KW  - fungicide
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147396
VL  - 3
ER  - 
TY  - JOUR
A1  - Kunz, Meik
A1  - Liang, Chunguang
A1  - Nilla, Santosh
A1  - Cecil, Alexander
A1  - Dandekar, Thomas
T1  - The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development
JF  - Database
N2  - The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure–activity relationships.
KW  - drug-minded protein
KW  - database
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147369
VL  - 2016
ER  -