Senior Scientist in Structural Biology at Vernalis; R&D Ltd

Senior Scientist in Structural Biology at Vernalis (R&D) Ltd, Cambridge, UK

United Kingdom

Working within our fully equipped research laboratories in Cambridge, our established group of scientists are world leaders in multiple hit- and structure-based drug discovery. Our scientists leverage cutting edge lead generation and structure based design to unlock new possibilities in drug discovery, advancing innovative compounds towards development candidates across diverse therapeutic areas, including oncology, neurodegeneration, anti infectives and inflammation.

We are seeking a highly motivated Senior Scientist in structural biology to support our drug discovery programs. Your expertise in protein crystallography will be instrumental in solving multiple ligand bound protein structures, understanding protein ligand interactions to accelerate the identification and optimization of high-quality lead compounds. This is a hands on role covering the full spectrum of a protein crystallography study including construct design, protein crystallisation, crystallographic data collection, structure solution and refinement, structural analysis, and reporting.

You will contribute to hit identification and validation strategies and help enable high throughput structure determination workflows. You will collaborate across multiple disciplines including computational chemistry, biophysics, and medicinal chemistry teams with both internal and external collaborators and play a key part in shaping research directions and advancing structure guided drug discovery projects.

• Use protein crystallography to solve high resolution apo and ligand bound structures of protein targets.
• Identify potential binding sites, interpret ligand binding mechanisms, and optimise small molecule interactions with protein targets.
• Identify starting points for drug development. Design, execute and interpret high throughput crystallography screens of compound libraries, followed by optimisation and hit expansion.
• Integrate structural insights into the wider drug discovery pipeline, working closely with medicinal chemistry, biophysics and computational biology teams.
• Provide structural rationale for the design and modification of small molecules that target key proteins involved in disease.
• Stay at the forefront of new structural biology methodologies, particularly in ligand binding and FBDD. Develop and optimise protocols to increase throughput, improve structural data quality and streamline workflows.
• Collaborate cross functionally with internal teams and external partners across drug discovery projects.
• Present project data, scientific interpretation and strategy internally and to external collaborators.
• Represent Vernalis at scientific conferences.
• Assist in the training and supervision of students and junior team members.

Essential Qualifications &

Experience:

• PhD in Structural Biology, Biophysics or a related field, with postdoctoral or industrial experience in drug discovery and structural biology techniques, particularly in relation to protein-ligand interactions and fragment based drug discovery.
• Experience in high throughput crystallographic screens and the use of advanced software, such as COOT, CCP4i2, PanDDA, to determine and refine large numbers of protein ligand complexes.
• Experience in rapid fitting of ligands to density maps, with consideration of ligand occupancy states and alternative conformation analysis.
• Strong understanding of ligand chemistry including ligand geometries, low energy conformations, chirality, protonation and tautomeric states, and bond orders.
• Experience in protein crystallisation screening experiments using robotics and commercial crystallisation screens.
• Experience in protein ligand complex formation by co crystallisation and soaking experiments, including cryoprotectant determination and cryo freezing for in house and synchrotron data collection.
• Ability to work effectively in a dynamic, fast paced research environment.
• Excellent communication, collaboration and project management skills.
• Experience of cryo EM sample preparation and data analysis.
• Familiar it…