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The Director of CEITEC MU opens position:
Post-doc position in biomololecular simulations
Faculty:
Central European Institute of Technology, Masaryk University
Application deadline: May 31st 2015
Title: Calculation of binding affinities of phosphopeptides towards 14-3-3ζ that are important in
neurobiochemistry of the brain.
Project Description
14-3-3 proteins play key role in the neurobiochemistry of brain and are also associated with neurodegenerative
amyloid diseases such as Alzheimer and Parkinson disease. 14-3-3 proteins bind more than 850 diverse target
phosphoproteins, thereby forcing conformational changes or/and stabilizing active conformations in their target
proteins. However, the preparation of high quantities of phosphorylated samples in high concentrations, needed for
experimental measurement of binding affinities, is usually very difficult. Therefore, this task will be addressed by the
accurate free energy calculations that represent an attractive alternative to the highly demanding experimental
determination of the binding affinities.
The main aim of this post-doctoral project is the calculation of binding affinities of phosphorylated peptides in the
complex with 14-3-3. Different schemes of Hamiltonian replica exchange molecular dynamics (H-REMD) will be
applied to a set of phosphopeptides bound to 14-3-3 and calculate their absolute binding affinities. The binding
affinities obtained from the potential of mean force of small peptides binding to 14-3-3 will be compared to
experimental binding affinities measured by ITC and NMR titration experiments.
Desired expertise and skills
Suitable candidates should have strong background in biomolecular simulations. Experience in enhanced sampling
techniques and free energy calculations are considered an asset.
We offer
 Motivating environment in a young, international and multidisciplinary team in CEITEC.
 Starting date: negotiable.
Electronic applications are expected by 31/05/2015
Please e-mail a letter of motivation and your CV in English including the list of publications and recommendations
of two research scientists by e-mail to Dr. Jozef Hritz, [email protected]
Selected references:
Hritz J.; Byeon I-J.; Krzysiak T.; Martinez A.; Sklenář V.; Gronenborn A.M. Dissection of binding between a
phosphorylated tyrosine hydroxylase peptide and 14-3-3ζ: a complex story elucidated by NMR.
Biophys. J. 2014, 107, 2185-2194
Hritz,J.; Oostenbrink, C. Efficient free energy calculations for compounds with multiple stable conformations
separated by high energy barriers. J. Phys. Chem. B 2009, 113, 12711-12720
More information about CEITEC on http://www.ceitec.eu/
Masaryk University | IN: 00216224
Central European Institute of Technology
Kamenice 753/5, CZ-62500 Brno, Czech Republic
www.ceitec.muni.cz | [email protected]