Computational methods in chemistry speed up the discovery of bioactive compounds and make lab work cheaper and more effective. This starts with the automated mining and analyses of public data and boils down to molecular interaction modelling.
Here we concentrate on the latter part exemplified by the development plant PARP-enzyme inhibitors as potential agrochemicals that enhance the survival and yield of crops under drought stress (cf. climate change). The same works for human drugs (e.g. human PARP is an anticancer target).
Following the initial generation of a three-dimensional model of a protein target, millions of structures in different conformations are docked and filtered for interaction quality, availability and other properties in a virtual screening procedure. A resulting set of actual compounds is then evaluated in a new bioassay that does not require spraying of plants. It is the first test for drought stress tolerance that uses sterile plant clones in microtiter plates, is fully quantifiable, and concentration dependent.
Wessjohann Group | Leibniz Institute of Plant Biochemistry, Halle, Germany
Ludger Wessjohann is managing director of the Leibniz Institute of Plant Biochemistry and head of the Department “Bioorganic Chemistry”. He has published more than 300 papers and filed over 20 original patents. His interests span the discovery and development of new bioactive compounds, from isolation to total synthesis and mode of action studies. Modern computational, chemoenzymatic and synthetic biology methods play a crucial role in this.
Wolfgang Brandt is head of computational chemistry in the Wessjohann group. He is an expert in protein structure modelling and MM/QM calculations.
Peter-Paul Heym is a PhD-student in the Wessjohann group specialized on homology modelling and virtual screening useful for the development of agrochemicals.
Robert Berger is a trained food chemist, now working on his PhD-thesis to discover phytoeffectors in planta, especially drought stress tolerance enhancers. He develops assays, synthesizes derivatives (not shown) and analyses treated vs. untreated plant proteomes (not shown) to discover the responsible protein targets.
Virtual Screening general:
Tennstedt, S., Fischer, J. Brandt, W., Wessjohann, L. in: Virtual screening – tools for a faster selection of new drug leads”. Medicinal Chemistry in Drug Discovery – Review Book, 2013: 219-236 (Ed. Dubravko Jelić), Transworld Research Network (37/661 (2), Fort P.O., Trivandrum-695 023, Kerala, India), ISBN: 978-81-7895-560-5
Bobach, C., Tennstedt, S., Palberg, K., Denkert, A., Brandt, W., de Meijere, A., Seliger, B., Wessjohann, L.: Screening of synthetic and natural product databases: Identification of novel androgens and antiandrogens; Eur. J. Med. Chem. 2015, 90, 267-279. . 10.1016/j.ejmech.2014.11.026 . doi: 10.1016/j.ejmech.2014.11.026
Heym, P-P.; Brandt, W.; Wessjohann, L.; Niclas, H-J.: Virtual screening for plant PARP inhibitors – what can be learned from human PARP inhibitors? Cheminform. 2012, 4 (Suppl 1), O-24. DOI: 10.1186/1758-2946-4-S1-O24.
Geissler, T.; Wessjohann, L.; A whole plant microtiter plate-assay for drought stress tolerance inducing effects? J. Plant Growth Regul. 2012, 30, 504-511. DOI: 10.1007/s00344-011-9212-1.
Data mining and cheminformatics:
For a free demo search and analytics engine (basic tools only) go to: www.ocminer.com
. Try e.g. “analytics: co-occurences” to test data concept, analysis and automatic relationship tools. For more detailed info visit www.ontochem.com (commercial).
Wessjohann, L.; Ruijter, E.; Garcia-Rivera, D.; Brandt, W.: “What can a chemist learn from nature’s macrocycles? A brief, conceptual view”; Mol. Diversity 2005, 9 (1) 171-186.
Multicomponent reaction II
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