Platforms

Protein Structure & Biophysics

Introduction

Understanding protein-ligand interactions is pivotal for accelerating lead identification and structure guided lead optimisation. Our team of experts at the X-ray crystallography (X-RAY) platform support the determination of high-resolution structures of proteins and protein-ligand complexes.

The X-ray team provides solutions tailored to your needs starting from construct design, protein expression & purification, HTS for crystal hit identification & optimisation of crystallisation conditions to atomic structure solution. The X-ray team has access to both in-house diffractometers and commercial beamline at synchrotrons to provide fast turn around to your projects. Experienced crystallographers with expertise on various target proteins will work together with the clients.


Key Services

Construct Design and Optimisation:

Customised construct design to suit the client’s requirements will be offered. Further optimisation of affinity/expression tags, sequence coverage and site-directed mutagenesis  of the constructs can be performed based on client’s request.

Protein Expression and Purification:

  • Small scale expression screening
  • Large scale protein expression – LEX/shaker incubators
  • Protein purification – Akta Xpress (Affinity, ion exchange, gel filtration, tag cleavage)

Crystallisation Screens:

Once we obtain crystallisation grade protein, we screen for crystal hits using nanolitre liquid handlers (Mosquito ®).

 

Crystal Optimisation:

Once an initial hit is obtained we can optimise the protein concentration, incubation temperature, precipitants and additives. We can also do optimise through different seeding techniques and limited proteolysis of the protein.

 

Protein – Ligand Complexes:

  • Ligand-fragment, small-molecule, peptide, protein, DNA, co-factors
  • Optimisation of stabilisation solution and DMSO tolerance tests
  • Soaking ligands into apo crystals
  • Reverse soaking of ligand into  complex crystals
  • Co-crystallisation of protein-ligand complexes

 

Data Collection and Processing:

We have access to both in – house diffractometers and commercial synchrotron beamlines to test and improve diffraction quality. High resolution diffraction images are processed to obtain datasets.

 

Structure Solution and Interpretation:

Phase determination

Model building and refinement

Fitting ligands into electron density

Analysis of structures

 


Adaptability During COVID Era

  • Ensuring business continuity by diversifying synchrotron resources. Access to Japan, Australia and Taiwan synchrotrons – Have managed to efficiently adapt to changing COVID lockdown conditions in each country and plan shipments accordingly.
  • Proficient in working in team shifts.
  • Remote working through VPN incase of circuit breakers.


Our Experts

EARO ScD, Christophe Bodenreider
Head of XRAY, Nithya Baburajendran
Senior RF, Jothi Anantharajan
RA, Yeo Yee Khoon

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