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Master Thesis: Computational design of small molecules to treat neurodegenerative diseases

Advertising institute: IAS-5 - Computational Biomedicine
Reference number: D132/2015, Pharmaceutical Sciences, Chemistry, Physics

The section ‘Structural Neuroinformatics' INM-9/IAS-5 Computational Biomedicine at Forschungszentrum Jülich offers a dynamic and international work environment. Our lab develops and uses multi-scale simulation and structural bioinformatics tools to gain insights on important molecular events in signaling pathways. Collaboration with experimental labs around the world and industry is an important pillar of our work.

Computational chemistry is nowadays routinely used to accelerate the long and costly drug discovery process. Computations can help in all drug discovery phases, from drug target identification, commonly a receptor or an enzyme, to the design and optimization of a new drug-like compound. Goal of this Master project is to apply methods for structure-based drug design (SBDD) to targets of interest for the treatment of neurodegenerative disease. Targets for drug discovery include kinase proteins and specific nucleic acid structures, which have shown to be key for neurodegenerative disorders.

Computational methods such as docking, virtual screening, and de novo small molecules design will be employed to identify putative inhibitors of the selected target. Physicochemical variables that dictate the pharmacokinetics and drug-likeness of potent inhibitors will be also computationally evaluated and optimized. This means that absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) are key parameters that will be optimized to generate a drug candidate with good chances of success in clinical trials. Finally, molecular dynamics simulations will be utilized to gain further insights into the key interactions between the most promising ligands and the selected target, in order to recognize those inhibitors to be experimentally tested through external collaborations.

The general aims of this project are:
(i) Rational design of small molecules using Structure-Based Drug Design strategies;
(ii) Computational drug-likeness profile evaluation and optimization

We offer an excellent scientific infrastructure and technical assistance.

Students from the fields of Pharmaceutical Sciences, Chemistry, Physics or closely related disciplines are welcome to apply.
Familiarity with computational modeling, UNIX-like environments, and scripting/programming is desirable.

Please send your application to:
Forschungszentrum Jülich GmbH
INM-9/IAS-5 Computational Biomedicine
Dr. Marco De Vivo