Postdoctoral Fellow, Sweden

Project Title: Structure determination of ligands bound to a paramagnetically tagged target protein

Post Doc Location: AstraZeneca Mölndal, Sweden

Starting Date: January 2014 (24 months)

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. But we're more than one of the world's leading pharmaceutical companies. At AstraZeneca, we're proud to have a unique workplace culture that inspires innovation and collaboration. Here, employees are empowered to express diverse perspectives - and are made to feel valued, energized and rewarded for their ideas and creativity.

Main Supervisors:
AstraZeneca: Tomas Åkerud, Ph.D., Associate Principle Scientist, Structure and Biophysics, Discovery Sciences, Sweden
Leiden University: Marcellus Ubbink, Professor, Institute of Chemistry, Section Protein Chemistry, The Netherlands
University of Florence: Claudio Luchinat, Professor, CERM Magnetic Resonance Center, Italy

Description of Opportunity:
We have an exciting opportunity for a Ph.D. scientist to develop methodology to determine the orientation of ligands bound to proteins of pharmaceutical interest. The aim of the work is to produce information that is complementary to conventional methods for structure determination of protein-ligand complexes. This should enable more efficient synthetic chemistry efforts in a drug discovery programme. The work is multi-disciplinary in nature and includes secondments to Leiden University and the University of Florence, research centres with extensive experience in paramagnetic protein NMR.

This position is part of the FP7 - PEOPLE Marie Curie Initial Training Network "pNMR" (Pushing the Envelope of Nuclear Magnetic Resonance Spectroscopy for Paramagnetic Systems. A Combined Experimental and Theoretical Approach). For more information please visit http://www.pnmr.eu/ (the "Jobs"-tab).

The role's main objectives
-To enable more efficient synthetic chemistry efforts in drug discovery by determining the relative orientation of small molecule ligands to at least one drug target protein
-To show that this can be achieved within a time-frame that is compatible with the time-lines in a drug-discovery programme
The role's major responsibilities
-Show strong initiative in conducting research, and bringing it to functional use within AstraZeneca and the drug discovery community
-Interface with scientists from across many disciplines while at the same time being able to work independently
-Strong written and oral communication skills
-Ability to work effectively with colleagues and initiate collaboration

Tasks and methodology
-Production of drug target protein with lanthanide binding tags rigidly attached
-Determination of pseudo-contact shift (PCS) tensors for the lanthanide tagged proteins
-Detection of transferred PCSs for several ligands
-Structure calculations based on PCSs. Comparison with known crystal structures to assess quality of PCS-based structures

Minimum experience
A PhD in biomolecular NMR or closely related field

Preferred experience/requirements
-Protein NMR assignments
-Protein-ligand interactions and binding kinetics
-Protein production
-Paramagnetic NMR
-Synthetic chemistry

More information

For more information about the position please contact Tomas Åkerud at +46 31 7064412